Respiratory effort detection method and apparatus

ABSTRACT

A method of predicting critical points in patient respiration includes monitoring at least one characteristic of a respiratory effort waveform of a patient to detect a respiratory event. A refractory period is defined that includes a hard refractory period during which time the respiratory event cannot be responded to and a soft refractory period following the hard refractory period. The respiratory event outside of the refractory period is detected as a function of a first set of predetermined parameters for the monitored at least one characteristic and the respiratory event within the soft refractory period is detected as a function of a second set of predetermined parameters for the monitored at least one characteristic. The respiratory event may be inspiration onset and the characteristic of the respiratory effort waveform monitored is at least one of slope and amplitude. The refractory period may be defined based on detection of inspiration offset and further may be defined based on inspiration offset, an average respiratory period, and an average time of inspiration. Further, stimulation may be provided in response to a detected inspiration onset. Another method of predicting critical points includes sampling the amplitude of the respiratory effort waveform of a patient. A sample signal is generated representative of at least one characteristic of the respiratory effort waveform based on each amplitude sample. The sample signals representative of the at least one characteristic of the respiratory effort waveform are monitored and a respiratory event is detected as a function of at least two sample signals. Apparatus and systems for use with such methods are also described.

FIELD OF THE INVENTION

The present invention relates generally to medical devices and methodsfor use in the treatment of respiratory disorders. More particularly,the present invention pertains to methods of detecting respiratoryeffort for use in the treatment of respiratory disorders and devicesregarding same.

BACKGROUND OF THE INVENTION

Sleep apnea, an airway disorder, has been known for some time as amedical syndrome in two generally recognized forms. The first is centralsleep apnea, which is associated with the failure of the body toautomatically generate the neuromuscular stimulation necessary toinitiate and control a respiratory cycle at the proper time. Workassociated with employing electrical stimulation to treat this conditionis discussed in Glenn, "Diaphragm Pacing: Present Status", Pace, V.I, pp357-370 (July-September 1978).

The second sleep apnea syndrome is known as obstructive sleep apnea.Ordinarily, the contraction of the dilator muscles of the upper airways(nose and pharynx) allows their patency at the time of inspiration. Inobstructive sleep apnea, the obstruction of the airways results in adisequilibrium between the forces which tend to collapse airways(negative inspiratory transpharyngeal pressure gradient) and those whichcontribute to their opening (muscle contraction). The mechanisms whichunderlie the triggering of obstructive apnea include a reduction in thesize of the superior airways, an increase in their compliance, and areduction in the activity of the muscle dilator. The muscle dilators areintimately linked to the respiratory muscles and these muscles respondin a similar manner to a stimulation or a depression of the respiratorycenter. The ventilatory fluctuations observed during sleep (alternatelyhyper and hypo ventilation of periodic respiration) thus favors aninstability of the superior airways and the occurrence of oropharyngealobstruction. In sleep apnea the respiratory activation of thegenioglossus muscle has been particularly noted to be ineffective duringsleep. The cardiovascular consequences of apnea include disorders ofcardiac rhythm (bradycardia, auriculoventricular block, ventricularextrasystoles) and hemodynamic (pulnonary and systemic hypertension).This results in a stimulatory metabolic and mechanical effect on theautonomic nervous system. The syndrome is therefore associated with anincreased morbidity (the consequence of diurnal hypersomnolence andcardiovascular complications).

A method for treatment of sleep-apnea syndrome is to generate electricalsignals to stimulate those nerves which activate the patient's upperairway muscles in order to maintain upper airway patency. For example,in U.S. Pat. No. 4,830,008 to Meer, inspiratory effort is monitored andelectrical signals are directed to upper airway muscles in response tothe monitored inspiratory effort. Or, for example, in U.S. Pat. No.5,123,425 to Shannon, Jr. et al., a collar contains a sensor to monitorrespiratory functioning to detect an apnea episode and an electronicsmodule which generates electrical bursts to electrodes located on thecollar. The electrical bursts are transferred transcutaneously from theelectrodes to the nerves innervating the upper airway muscles. Or, forexample, in U.S. Pat. No. 5,174,287 issued to Kallok, sensors monitorthe electrical activity associated with contractions of the diaphragmand also the pressure within the thorax and the upper airway. Wheneverelectrical activity of the diaphragm suggests that an inspiration cycleis in progress and the pressure sensors show an abnormal pressuredifferential across the airway, the presence of sleep apnea is assumedand electrical stimulation is applied to the musculature of the upperairway. Or, for example, in U.S. Pat. No. 5,178,156 issued to Wataru etal., respiration sensing includes sensors for sensing breathing throughleft and right nostrils and through the mouth which identifies an apneaevent and thereby triggers electrical stimulation of genioglossusmuscle. Or, for example, in U.S. Pat. No. 5,190,053 issued to Meer, anintra-oral, sublingual electrode is used for the electrical stimulationof the genioglossus muscle to maintain the patency of an upper airway.Or, for example, in U.S. Pat. No. 5,211,173 issued to Kallok et al.,sensors are used to determine the effectiveness of the stimulation ofthe upper airway and the amplitude and pulse width of the stimulationare modified in response to the measurements from the sensors. Or, forexample, in U.S. Pat. No. 5,215,082 issued to Kallok et al., uponsensing of the onset of an apnea event, a stimulation generator providesa signal for stimulating the muscles of the upper airway at a varyingintensity such that the intensity is gradually increased during thecourse of the stimulation. Or, for example, in U.S. Pat. No. 5,483,969issued to Testerman et al., stimulation of an upper airway muscle issynchronized with the inspiratory phase of a patient's respiratory cycleusing a digitized respiratory effort waveform. A fully implantablestimulation system is described in Testerman et al. with a sensorimplanted in a position which has pressure continuity with theintrapleural space such as the suprasternal notch, the space between thetrachea and esophagus or an intercostal placement.

However, even with these modes of respiratory disorder treatment, thereremain many practical difficulties for implementing them and othertherapy treatments in medically useful systems. In particular, ifstimulation for respiratory disorder treatment occurs in response todetected points of a respiratory effort waveform, it is important to beable to accurately and reliably detect such critical points. Forexample, if stimulation for treating sleep apnea is to begin within apredetermined period of time of inspiration onset and no later than, forexample, 200 ms after inspiration onset in order to avoid airwayobstruction prior to stimulation, accurate detection is required.Although various techniques have been used for detecting critical pointsfor initiating stimulation, such as, for example, in Testerman et al.,there is always a need in the art for other and/or improved methods anddevices for detection of such critical points and systems for treatmentusing such detection.

SUMMARY OF THE INVENTION

A method of predicting critical points in patient respiration inaccordance with the present invention is described. The method includesmonitoring at least one characteristic of a respiratory effort waveformof a patient to detect a respiratory event. A refractory period isdefined that includes a hard refractory period during which time therespiratory event cannot be responded to and a soft refractory periodfollowing the hard refractory period. The respiratory event outside ofthe refractory period is detected as a function of a first set ofpredetermined parameters for the monitored at least one characteristicand the respiratory event within the soft refractory period is detectedas a function of a second set of predetermined parameters for themonitored at least one characteristic.

In one embodiment of the method, the respiratory event is inspirationonset. Further, the at least one characteristic of the respiratoryeffort waveform monitored is at least one of slope and amplitude.

In another embodiment of the method, the step of detecting inspirationonset outside of the refractory period includes detecting inspirationonset as a function of monitored slope of the respiratory effortwaveform. Further, the step of detecting inspiration onset within thesoft refractory period includes detecting inspiration onset as afunction of monitored slope and amplitude of the respiratory effortwaveform.

In another embodiment of the method, the refractory period is definedbased on detection of inspiration offset. Further, the inspirationoffset is detected as a function of the monitored slope and amplitude ofthe respiratory effort waveform. Yet further, the detection ofinspiration offset includes validating the detected inspiration offsetby comparing the amplitude of the sampled respiratory waveform to avalidating offset threshold.

Moreover, in another embodiment, the refractory defining step includesdetecting inspiration offset, determining an average respiratory period,and providing an average time of inspiration. The refractory period,including the soft and hard refractory periods, are defined as afunction of the detected inspiration offset, average respiratory period,and average time of inspiration.

A method for providing stimulation of a patient to treat respiratorydisorders in accordance with the present invention includes monitoringslope and amplitude of a respiratory effort waveform of a patient todetect inspiration onset. A refractory period is defined including ahard refractory period during which time an inspiration onset cannotinitiate stimulation and a soft refractory period following the hardrefractory period. An inspiration onset outside of the refractory periodis detected as a function of the slope of the respiratory effortwaveform and an inspiration onset within the soft refractory period isdetected as a function of slope and amplitude of the respiratory effortwaveform. Stimulation is provided in response to a detected inspirationonset.

In one embodiment of the method, the refractory period is defined basedon detection of inspiration offset. Further, inspiration offset isdetected as a function of the monitored slope and amplitude of therespiratory effort waveform.

In another method for providing stimulation of a patient to treatrespiratory disorders, the method includes monitoring slope andamplitude of a respiratory effort waveform of a patient to detectinspiration onset and inspiration offset. A refractory period is definedthat includes a hard refractory period during which time an inspirationonset cannot initiate stimulation and a soft refractory period followingthe hard refractory period. An inspiration onset is detected outside ofthe refractory period as a function of a first set of at least one ofslope and amplitude criteria for the respiratory effort waveform and aninspiration onset is detected within the soft refractory period as afunction of a second set of at least one of slope and amplitude criteriafor the respiratory effort waveform. Stimulation is provided in responseto detection of inspiration onset. The stimulation terminates as afunction of detection of inspiration offset or a maximum stimulationtime. The second set of criteria is set sufficiently sensitive relativeto the first set of criteria such that stimulation, for one or morerespiratory cycles, is applied as a function of the maximum stimulationtime and the defined refractory period.

In another method of predicting critical points in patient respiration,the method includes sampling the amplitude of the respiratory effortwaveform of a patient. A sample signal is generated representative of atleast one characteristic of the respiratory effort waveform based oneach amplitude sample. The sample signals representative of the at leastone characteristic of the respiratory effort waveform are monitored anda respiratory event is detected as a function of at least two samplesignals.

An apparatus for predicting critical points in patient respiration inaccordance with the present invention is also described. The apparatusincludes monitoring means for monitoring at least one characteristic ofa respiratory effort waveform of a patient and respiration detectionmeans for detecting a respiratory event. The respiration detection meansincludes means for defining a refractory period including a hardrefractory period and a soft refractory period following the hardrefractory period, means for detecting the respiratory event outside ofthe refractory period as a function of a first set of predeterminedparameters for the monitored at least one characteristic of therespiratory effort waveform, and means for detecting the respiratoryevent within the soft refractory period as a function of a second set ofpredetermined parameters for the monitored at least one characteristicof the respiratory effort waveform.

In various embodiments, the respiratory event may be inspiration onset,the at least one characteristic of the respiratory effort waveformmonitored is at least one of slope and amplitude of the respiratoryeffort waveform, and/or the respiration detection means may includemeans for detecting inspiration offset as a function of the at least onemonitored slope and amplitude of the respiratory effort waveform.

A system for providing stimulation of a patient to treat respiratorydisorders in accordance with the present invention is also described.The system includes a sensor for providing a signal characteristic of arespiratory effort waveform of the patient, slope monitoring means formonitoring the slope of the respiratory effort waveform, amplitudemonitoring means for monitoring the amplitude of the respiratory effortwaveform, and respiration detection means for detecting inspirationonset. The respiration detection means includes means for defining arefractory period including a hard refractory period during which timean inspiration onset cannot be responded to and a soft refractory periodfollowing the hard refractory period, means for detecting inspirationonset outside of the refractory period as a function of the slope of therespiratory effort waveform, and means for detecting inspiration onsetwithin the soft refractory period as a function of slope and amplitudeof the respiratory effort waveform. The system further includes meansfor generating a stimulation signal in response to a detectedinspiration onset and at least one electrode for delivering thestimulation signal to the patient.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a side sectional diagram of a patient having normalrespiratory activity.

FIGS. 2a-c are graphs of normal respiratory waveforms (shown with fullnormal inspiration at the peak). FIG. 2a shows a respiratory effortwaveform and indicated phases of the respiratory effort waveform. FIG.2b shows a graph of a respiratory airflow waveform with FIG. 2c showingthe corresponding respiratory effort waveform.

FIG. 3 is a side sectional diagram of the patient of FIG. 1 at the onsetof obstructive apnea.

FIGS. 4a and 4b are respiratory waveforms of inspiratory effort showingnormal inspiratory effort (FIG. 4a) and the change in normal inspiratoryeffort at the onset of an apnea event (FIG. 4b). FIG. 4c is arespiratory waveform showing respiratory airflow (as opposed to therespiratory effort waveform shown in FIGS. 4a and 4b) in a patientduring an apnea event.

FIG. 5 is a front sectional diagram of a patient showing the implantablecomponents of the stimulation system in accordance with the presentinvention.

FIG. 6 is a block diagram of the stimulation system shown in FIG. 5further including physician and patient programming units.

FIG. 7 is a diagram of one embodiment of the physician programming unitshown in block form in FIG. 6.

FIG. 8 is a diagram of one embodiment of the patient programming unitshown in block form in FIG. 6.

FIG. 9 is a diagram showing one embodiment of the IPG/stimulator shownin block form in FIG. 6.

FIGS. 10a-10e are illustrations showing various positions orconfigurations for mounting the sensor shown in block form in FIG. 6 forsensing respiratory effort at a position in proximity to the posteriorsurface of the manubrium.

FIGS. 11a-11d are various views of one embodiment of the sensor shown inblock form in FIG. 6. FIG. 1 la is a side view of the sensor, FIG. 11bis a cutaway view showing the sensing element portion of the sensor withthe sleeve subassembly of the sensor cut partially away, FIG. 11c is across-section view of the sensing element portion of the sensor, andFIG. 1d is a cross-section view of the connector portion of the sensor.

FIG. 12a is a first embodiment of a block diagram of the signalprocessing circuitry of the IPG/stimulator shown in block form in FIG.6, implemented in logic, for receiving the respiratory effort signalfrom the sensor and providing an inspiration synchronized stimulationsignal to the electrode in accordance with the present invention.

FIG. 12b is a second embodiment of a block diagram of the signalprocessing circuitry of the IPG/stimulator shown in block form in FIG.6, implemented with a microprocessor, for receiving the respiratoryeffort signal from the sensor and providing an inspiration synchronizedstimulation signal to the electrode in accordance with the presentinvention.

FIG. 13a is a top level flow diagram of the algorithm/control logicshown in block form in FIG. 12a and 12b in accordance with the presentinvention.

FIG. 13b is a flow diagram of the IPG-ON block of the flow diagram ofFIG. 13a.

FIG. 13c is a flow diagram of the Onset Detection block of the flowdiagram of FIG. 13a.

FIG. 13d is a flow diagram of the Offset Detection During Stimulationblock of the flow diagram of FIG. 13a.

FIG. 13e is a flow diagram of the Offset Detection block of the flowdiagram of FIG. 13a when stimulation is not occurring.

FIG. 13f is a flow diagram of the Suspension, Artifact, Therapy Delayblock of the flow diagram of FIG. 13a.

FIG. 13g is a flow diagram of the AGC Adjust block of the flow diagramof FIG. 13a.

FIG. 14 is a graph showing a normal respiratory effort waveformindicating various critical points detected in accordance with thepresent invention, various thresholds used in such detection, a normaldifferential pressure signal, a stimulus signal synchronously appliedbased on the critical points detected with respect to the respiratoryeffort waveform, and an illustration showing the definition of arefractory period, all in accordance with the present invention.

FIG. 15 is a graph showing a respiratory effort waveform having anartifact therein, a stimulus signal applied according to the presentinvention, and an illustration of the refractory period utilized toreject the artifact as an inspiration onset, all in accordance with thepresent invention.

FIG. 16a shows a normal respiratory effort waveform and stimulus appliedaccording to the present invention. FIG. 16b shows a respiratory effortwaveform of a patient with central sleep apnea and a stimulus appliedaccording to the present invention utilizing a maximum stimulation timelimit in accordance with the present invention. FIG. 16c shows a centralsleep apnea occurring between cycles of respiratory effort. FIG. 16dillustrates stimulation periods for treatment of the central sleep apneaoccurring in FIG. 16c. FIG. 16e shows AGC gain for the respiratorysignal shown in FIG. 16c during the central sleep apnea.

FIGS. 17a-c are graphs of one embodiment of a stimulation burst used forstimulating the patient according to the present invention.

FIG. 18 is a block diagram of one embodiment of a microprocessor basedstimulation system.

FIG. 19 is a block diagram illustration of one diagnostic self teststrategy for a therapy system.

FIGS. 20a-d are block diagrams of various internal diagnostic self testsfor the system shown in FIG. 18.

DETAILED DESCRIPTION OF THE EMBODIMENTS

The following description relates generally to therapy systems includingimplantable therapy and stimulation systems. Although many portions ofthis description are particularly applicable to the treatment ofrespiratory disorders, such as sleep apnea, by administering stimulationof musculature in synchrony with detected periodic events of therespiratory cycle, many portions of the system are equally applicable toother therapy systems. For example, automatic gain control, diagnostictesting, and methods for conserving energy are applicable to one or moreother therapy systems such as, for example, drug delivery systems, blinkstimulation systems, and cardiac related systems.

With respect to the synchronization of stimulation to the respiratorycycle of a patient to treat respiratory disorders, such synchronizedstimulation requires a suitable respiratory sensor, proper placement ofthe respiratory sensor, and signal processing capability for convertingthe sensed respiratory effort signal from the sensor to a stimulationsignal for use in stimulating the patient. In FIG. 1 and FIGS. 2a-c,normal respiratory activity is depicted. In FIG. 1, a patient 10 has anairway 15 which remains patent during inspiration of air 20. FIG. 2ashows a typical respiratory effort waveform for two complete respiratorycycles. This analog waveform can be generated by various transducerssuch as, for example, a belt transducer worn snugly about the chest ofthe patient as used for detection and analysis of sleep apnea in sleeplaboratories, an implanted pressure sensor such as that described indetail below, or any other transducer that provides a respiratory effortsignal adequate for analysis to detect critical points thereof for usein the treatment of respiratory disorders, such as sleep apnea. Eachwave of the waveform is characterized by a negative peak 30 oncompletion of expiration, a positive peak 35 on completion ofinspiration (i.e. inspiration offset) and a turning point 40 whichindicates the onset of inspiration (i.e. inspiration onset). Each waveof the waveform can therefore be separated into a period of respiratorypause 32, an inspiratory phase 33 and an expiratory phase 34.Respiratory effort waveforms having similar identifiable characteristicscan be provided by monitoring other physiological signals such asintrathoracic pressure, intrathoracic impedance or electromyographicpotentials. Other characteristics of the waveform could also beidentified in connection with tracking and analyzing the respiratorywaveform to monitor respiratory activity in sleep apnea treatment. Innormal respiration, the respiratory effort waveform is related toairflow as set forth in FIGS. 2b and 2c. In FIG. 2b a trace of normalrespiratory airflow from a flow transducer is shown while FIG. 2c showsthe corresponding trace of the normal respiratory effort which producesthe airflow.

In FIGS. 3 and 4b, respiration in the same patient at the onset of anobstructive sleep apnea event is depicted. FIG. 3 shows the patient 10and airway 15 with an airway obstruction 17 that is characteristic of anobstructive apnea event. FIG. 4a shows that in a normal respiratoryeffort waveform 43, the inspiratory peaks 45a-d are of approximately thesame amplitude. By comparison in FIG. 4b, in a waveform 47, theinspiratory peaks 48a-d become significantly greater in amplitude at theonset of obstructive apnea than the immediately preceding inspiratorypeak 49. This is reflective of the increased inspiratory effortundertaken by the patient in response to the difficulty of breathingthrough the obstructed airway.

In treatment of sleep apnea, the increased respiratory effort is avoidedby synchronized stimulation of a muscle which holds the airway openduring the inspiratory phase. Preferably, the muscle stimulated is anupper airway muscle, such as the genioglossus muscle stimulated by acuff electrode placed around the hypoglossal nerve. However, there maybe other upper airway muscles or nerves which can be used forstimulation to perform the same function and also other nerves ormuscles apart from the upper airway which may be stimulated, such as thediaphragm, to treat respiratory disorders, such as, for example, sleepapnea. The effect of this stimulation on obstructive sleep apnea can beseen in the airflow trace of FIG. 4c. During a first period indicated as46a, stimulation is enabled producing a normal respiratory airflow.During a second period indicated as 46b, stimulation is disabled causingobstruction of the airway and reduction in airflow volume (apnea).During a third period indicated as 46c, stimulation is resumed,restoring patency to the airway and increasing airflow volume.

Components, and one implantable configuration, of an implantablestimulation system 50 for providing inspiration synchronous stimulationtreatment of sleep apnea are shown in FIG. 5. A block diagram of thesecomponents and other associated programming components of the system 50for treating sleep apnea is shown in FIG. 6. As shown in FIG. 5,inspiration synchronous stimulation is controlled by the implantablepulse generator (IPG)/stimulator 55. IPG 55, also shown in FIG. 9,provides inspiration synchronized stimulation, e.g. one or morestimulation pulses, through stimulation lead 52 to an electrode orelectrode system 65 placed around the hypoglossal nerve 53 forstimulation of the genioglossus muscle of the upper airway. Theelectrode or electrode system 65 may be positioned with respect to anyother respiratory nerve, or other nerve or muscle that provides thedesired stimulation result for the respiratory disorder treated. The IPG55, i.e. stimulator/controller, receives respiratory effort waveforminformation via a sensor lead 57 from a respiratory sensor or transducer60 sensing the respiratory effort of a patient 10.

One associated component of system 50 includes a physician programmer80, such as a laptop computer having programming software andcommunication capabilities for communicating with the IPG 55, and whichis capable of programming the IPG 55 with various parameters in order toadapt the system for treatment of a particular patient. The system 50 ofFIG. 5, is therefore adapted to be programmed using the physicianprogrammer 80 as shown in FIG. 7 by telemetry via transmitting/receivingelement 81 electrically coupled to the processor based programmer 80.Thereafter, the system 50 is used each night by the patient to preventthe closure of the upper airway during the inspiratory phase of therespiration cycle.

It will be apparent to those skilled in the art that such a system mustbe made to be easy to use by the patient and since it is used withoutconstant medical supervision, it must be able to adapt to many differentoperating conditions. Therefore, the system 50 includes anotherassociated component, i.e. patient programmer 70, as shown in FIG. 8.The patient programmer 70 gives the patient the capability to turn thestimulator ON/OFF, adjust the stimulation amplitude within preset limitsprogrammed by the physician and adjust any other stimulation parametersor parameters of the IPG 55 as may be allowed by the physician, such as,for example, stimulation pulse rate, pulse width, dose time, therapydelay time. The patient programmer 70 provides both a visual and audioconfirmation of communication with the stimulator and further mayinclude other patient control elements for controlling parameters of thetreatment of sleep apnea. In addition, as described further below, thepatient turning the power on for initiation of the treatment using thepatient programmer 70 starts an automatic self stimulation test and/oran automatic diagnostic self test of the components of the system 50.Such a diagnostic self test may be performed at any time, in addition tothe initiation of the treatment period by the patient. Further, suchself stimulation test and diagnostic tests are equally applicable toother therapy systems in addition to the treatment of respiratorydisorders, such as sleep apnea.

The pressure sensor or respiratory transducer 60, may be a dynamicrelative pressure sensor such as that disclosed in U.S. Pat. No.4,407,296 to Anderson or U.S. Pat. No. 4,485,813 issued to Anderson etal which are incorporated herein by reference in their entirety. Thepressure sensor 60 is surgically implanted in a region that has pressurecontinuity with the intrapleural space such as the suprasternal notch,the space between the trachea and esophagus or attached to either of thetrachea or esophagus, an intercostal placement, or secured as shown inFIGS. 10a-10e in a position for sensing pressure at the posterior sideof the manubrium as described in further detail below. The suprasternalnotch 62 and manubrium 63 of sternum 64 as shown in FIG. 5, are wellknown structures on the upper chest that are in anatomical continuitywith the intrapleural space. It is also well known that changes inintrapleural pressure provide a characteristic respiratory effortwaveform. The location for placement of the sensor is, at least in part,chosen as a function of delay, i.e. propagation time of a pressurewaveform characteristic of respiratory effort propagating from therespiratory point of origin to the sensor position and as a function ofthe amount of filtering necessary to achieve a usable sensed signal at aparticular location, i.e. filtering necessary to remove waveforms otherthan the waveform of the sensed characteristic, such as cardiac waveformactivity.

Preferably, the pressure sensor 60 utilized is a pressure sensorassembly or sensor lead 115 similar to the sensor lead sold under thetrade designation of Medtronic Model 4321, available from Medtronic,Inc., Mpls., Minn. as modified and represented in FIGS. 11a-11d. Thepressure sensor assembly 115 includes a sensing section 120, a leadanchoring section 122, and a connector section 124. A flexible lead body121 forms a part of each section. The sensing section 120 includes, asshown in the detail views of FIGS. 11b and 11c, a relative pressuresensing element 126 which is mounted at an open distal end 123 ofassembly 115 opposite the connector section 124. The relative pressuresensing element 126 senses respiration pressures through the use ofpiezo-electric crystals attached to a sensor diaphragm lyingperpendicular to a longitudinal axis 125 extending through assembly 115.Pressures are transmitted to the diaphragm through the portholes 128 onboth sides of the sensing element 126. Pressure transmits from theportholes 128 to the diaphragm via a medical adhesive 132, such assilicone rubber, which fills the nose cavity of the pressure sensingelement 126. The sensor is driven, for example, with a fixed biascurrent on which the AC pressure signal is coupled onto. Such a fixedsensor bias can range from about 8 μA to about 100 μA. Such a sensor hasa nominal output of about 3 mV/mmHg over the usable bandwidth of about0.1 to about 100 Hz.

The sensing element 126 has coil leads 136 electrically connectedthereto. The coil leads 136 are provided within bitumen tubing 138. Thebitumen tubing 138 at the sensor section end and the sensing element 126are positioned in a flexible tube 130 by medical adhesive 132 which alsofills the cone of the sensing element 126 and covers the outer portionsof the sensing element 126. There is no exposed metal surface of thesensing element 126 and the sensor is electrically isolated from thepatient.

As shown in FIG. 11d, a connector assembly 168, such as, for example, abipolar IS-1 compatible connector assembly, is electrically connected tothe lead body 121, such as by crimping, to coil leads 136 in connectorsection 124 of the sensor assembly 115. Any connector assembly may beutilized that is compatible with a connector port of the IPG 55. Theconnector includes sealing rings 167 to ensure that body fluids do notdisrupt the sensor assembly 115 and IPG 55 connection.

A sleeve attachment subassembly 140 has the sensing element 126 and aportion of the lead body 121 positioned therein. The sleeve subassemblyextends from a distal surface 174 of the sensing element 126 at the opendistal end 123 to beyond the interface between the lead body 121 andsensing element 126. The sleeve attachment subassembly 140 includes anouter threaded sleeve 142, an inner threaded sleeve 144, and a softumbrella ring 146. The sleeve attachment subassembly 140 is mounted onthe outer surface of the flexible tube 130 with medical adhesive 132.The inner surface of the inner threaded sleeve 144 is abraded to provideadhesion with the medical adhesive 132 to stably mount the sensingelement 126 in the subassembly 140. The inner threaded sleeve 144 hasholes 148 about the longitudinal axis therethrough for molding aflexible element, i.e. soft umbrella ring 146, about the distal open endof the inner threaded sleeve 144.

The soft umbrella ring 146 may be formed of silicone rubber and includesa flexible outer umbrella portion 152 that extends outward relative tothe longitudinal axis and rearwardly relative to the distal open end ofthe inner threaded sleeve 144 and a fixed portion 154 of the umbrellaring 146. The flexible outer umbrella ring 152 performs the function ofpreventing tissue and bone growth over the distal open end 123 of thesensor assembly 115 when implanted. The soft umbrella ring 146 ispreferably formed of a radio opaque material so that it can be seen inimaging processes throughout implantation and explanation. Further, theumbrella ring 146 may include a treatment to prevent tissue and boneovergrowth of the sensor 126. Such treatment may include treatment witha steroid, such as heparin, chemical coatings, surface roughening, orany other treatment that reduces such tissue and bone overgrowth.

The flexible element, i.e. umbrella ring 146, may be of anyconfiguration that prevents bone and tissue overgrowth. Further, if thesensor is implanted into a drill hole in the manubrium as describedbelow, the flexible element must be capable of being inserted andremoved through the drilled hole. For example, the flexible element maybe a donut shape or a simple flange extending outward relative to thelongitudinal axis 125 at the distal open end of inner threaded sleeve144.

The outer threaded sleeve 142 includes a threaded portion 156 and anunthreaded flange portion 158 extending substantially perpendicular toand outward relative to the longitudinal axis 125 of the sensor assembly115. The outer and inner threaded sleeves 142 and 144 are utilized foradjusting the length of the subassembly 140 along the longitudinal axis125. Further, they provide for anchoring the sleeve subassembly, i.e.securing the sensor, in the manubrium as described further below withthe unthreaded flange portion 158 of the outer threaded sleeve 142providing means for direct or indirect contact at the anterior side ofthe manubrium and with the flexible element 146 providing for direct orindirect contact at the posterior side of the manubrium. Theadjustability is important as the thickness of the manubrium varies frompatient to patient. One or more holes 160 in the flange portion 158 areavailable for anchoring the sensor section 120 by suture to tissue or bybone screw to the anterior side of the manubrium. The outer threadedsleeve 142 and the inner threaded sleeve 144 are preferably formed ofstainless steel, but can be any biocompatible material, preferably arigid biocompatible material.

In alternative configurations, the flange portion 158 may include a softcover thereabout or may be formed of a different shape as long as itstill performs the function of direct or indirect contact with themanubrium to hold the sensing element 126 in position and/or includesmeans for attachment by a bone screw, suture, or other securing means.For example, the flange portion 158 may be a tab structure or multipletabs extending away from and substantially perpendicular to thelongitudinal axis 125 from the end 159 of threaded portion 156.

Further, the adjustability function of the inner and outer sleeves 142and 144 may be provided by any structure that allows a length of thesleeve to be adjusted and then capable of being fixed at a particularlength. For example, two telescoping members or sliding members may beused with, for example, a ratchet technique coupling the two andproviding fixation at a particular length.

The anchoring section 122 includes lead body anchoring sleeve 164slidably mounted on the lead body 121 and having suture grooves 165 forthe anchoring of the lead body 121 when implanted. The lead body 121 isflexible such that it can make a sharp right angle from the sleevesubassembly 140 at the anterior region of the manubrium when the sensorassembly 115 is implanted to avoid skin erosion and bulge thereat. Forexample, the lead body 121 may include pentifilar conductor coils 136 ina bitumen silicon tubing. Alternatively, the lead body 121 may include aright angle attachment at the anterior region of the manubrium 63 forproviding direction to the lead body as it extends from the drilled holeat the anterior of the manubrium 63.

One skilled in the art will recognize that various connection techniquesfor connecting the sensing element 26 to the IPG 55 may be utilized. Forexample, fiber optic connection may be used, RF techniques may be used,and also techniques using the body mass itself to propagate a signalbetween components may be used. With use of at least some of theseconnection techniques, a lead extending from the anterior of themanubrium would not be present. Without the need for a lead, the sleevesubassembly 140 for positioning and anchoring the sensor in the drilledhole of the manubrium 63 could take the form of any mounting elementhaving an adjustable length. The mounting element would no longer needto have an opening therethrough, such as a sleeve, but could take theform of, for example, a spring loaded elongated member with one open endfor holding the sensor. In other words, the mounting elements used tomount the sensing element may take any elongated form with an adjustablelength and elements for securing it in the manubrium hole by direct orindirect contact with the anterior and posterior surfaces of themanubrium.

The pressure sensor 60, such as pressure sensor assembly 115, or anyother suitable sensor for providing a signal characteristic ofrespiratory effort, may be implanted in various positions, such as thosepreviously mentioned and further including attachment to the esophagusor trachea or in a position therebetween, or to any other soft tissue inthe suprasternal notch. Various positions for the sensor are describedin U.S. patent Ser. No. 08/310,177 entitled "Method and Apparatus ForDetecting and Treating Obstructive Airway Disorders" incorporated hereinby reference in its entirety. Further, the sensor 60 may be positionedas shown in the FIGS. 10a-10e. Preferably, the pressure sensor assembly115 is implanted through a drilled hole in the manubrium 63 as shown inFIGS. 10a and 10b. However, the sensor assembly 115 could be implantedthrough the sternum 64 at any location thereof or through any other bonesuch that the sensing element 126 is in communication with theintrathoracic region or a region with pressure changes characteristic ofrespiratory effort.

As shown in FIG. 10b, the brachiocephalic vein 195, also known as theinominant vein, is located in a region on the posterior side of themanubrium 63 and erosion of the vein is to be avoided. The presentinvention is configured to allow sensing in the region where this veinis located. The pressure sensor 60 is positioned in proximity to thevein, however, the term in proximity to the vein means that the sensingelement is positioned in the region of the vein but is configured and/orpositioned such that erosion of the vein is avoided.

To implant the pressure sensor assembly 115, a small pocket posterior tothe manubrium 63 via the suprasternal notch 62 is created, such as byblunt dissection. A hole 185 is drilled perpendicularly through thesuperior aspect of the manubrium 63 and at the midline of the manubrium63. It is desired that the sensor element 126, be placed near the top187 of the manubrium 63 so that the pocket created on the posterior sideof the manubrium 63 is minimized lessening surgical excavation risk andlessening the effects of cardiac signals which are stronger at lowerportions. Further, by implanting the sensor assembly 115 toward the topof the manubrium 63, the implanter can see the position of the umbrellaring 146 easily, especially with mirrors. During drilling, a retractoris placed on the posterior side of the manubrium 63 to protectintrathoracic structures. Although placement of the sensing element 126near the top 187 of the manubrium is preferred, the sensing element maybe positioned anywhere along the length of the sternum 64, although themanubrium is preferred. More preferably, the sensing element ispositioned about 0.5 cm to about 3 cm from the top 187 of the manubrium.

When implanting the sensor, the length of the sensor section 120 of thepressure sensor assembly 115 (i.e. length of subassembly 140) ismaximized by turning the outer threaded sleeve 142 with respect to theinner threaded sleeve 144 of the sleeve attachment subassembly 140. Thesleeve attachment subassembly 140 of the sensing section 120 is theninserted in the drilled hole 185 and the sensor section length isadjusted such that the soft umbrella ring 146 is in direct or indirectcontact with the posterior surface of the manubrium 63. When the sensorsection 120 is inserted into the drilled hole 185, the umbrella ring 146collapses or is compressed against the side of the sleeve subassembly140 and will spring outward upon protruding into the posterior side ofthe manubrium 63. The umbrella ring portion 152 will act as an anchorand will prevent bone and tissue growth over the sensor opening. Theimplanter can utilize a finger to make sure the umbrella ring 146 isflush with the posterior surface and to stabilize the sensor while theouter threaded sleeve 142 is turned to adjust the length of the sleeveattachment subassembly 140 of the sensor section 120 to the thickness ofthe patient's manubrium 63. The distal tip 174 of the sensing element126 should protrude in the range of about 1 mm to about 3 mm posteriorlyfrom the manubrium 63. A position less than 1 mm results in a greaterchance of tissue or bone overgrowth of the sensing element 126. Thedistal tip 174 of the sensing element 126 is flush with the open end ofthe inner threaded sleeve 144. The sensor assembly 115 can then beanchored on the anterior side of the manubrium by a suture or bone screwthrough the hole 160 of the unthreaded flange 158 of the outer threadedsleeve 142. The lead body 121 can be anchored with use of suture grooves165 on the anchoring sleeve 164.

With the IPG 55 implanted in a position on the upper chest, such as justbelow the clavicle 61 as shown in FIG. 5, the lead body 121 of thepressure sensor assembly 115 is inserted in a tunnel created from themanubrium 63 to a pocket created for implanting the IPG 55. When the IPG55 is implanted, the connector section 124 of the pressure sensorassembly 115 is connected to sensor port 58 of the IPG 55.

FIGS. 10c-10e show alternative configurations for implanting thepressure sensor 60 of the implantable stimulation system 50. As shown inFIG. 10c, a pressure sensor 60 has a sensing element 197 positionedposterior to the manubrium 63 with the lead body extending over the top187 of the manubrium 63. The lead is then brought down the anteriorportion of the manubrium 63. Various anchors 178 are utilized to holdthe sensing element 197 in place behind the manubrium 63.

As shown in FIG. 10d, the sensor 60 is positioned in a manner similar tothat shown with respect to the drill through technique described withreference to FIGS. 10a and 10b. However, in this configuration, thedrill hole 180 is made at an angle through the manubrium 63.

As shown in FIG. 10e, the sensor 60 is positioned substantially asdescribed in FIG. 10c. However, in order to protect against erosion offragile veins posterior of the manubrium, the sensing element 197 and aportion of the lead body extending therefrom are covered with a softguard 182. The guard 182 may serve the function of anchoring the sensor60 as well as preventing any erosion of the brachiocephalic vein 195.The distal end 196 of the guard is open.

As demonstrated by the various configurations shown, many variouspositions for implant of the sensor 60 are possible behind the manubriumyet while avoiding the fragile veins. The present invention contemplatesthe positioning and securing of various sensing elements with respect tothe manubrium 63 to sense pressure or any other characteristic forobtaining a respiratory effort waveform at a region posterior of themanubrium 63. The sensing elements are preferably placed in closeproximity to the posterior surface of the manubrium 63.

The electrode or electrode system 65 of the implantable stimulationsystem 50 may be any conventional electrode system for stimulation ofmuscles to treat respiratory disorders, such as sleep apnea. Aspreviously described, although various respiratory muscles may bestimulated, stimulation of the genioglossus muscle is utilized hereinfor treatment of sleep apnea. For example, the electrode system 65utilized may be a Model 3990B Half Cuff Nerve Electrode available fromMedtronic, Inc., Mpls., Minn. This electrode and other suitableelectrode configurations are described in U.S. Pat. No. 5,344,438 toTesterman et al., entitled "Cuff Electrode" and incorporated entirely byreference herein. This electrode is utilized for placement around arespiratory motor nerve, such as the hypoglossal nerve 53, with thestimulation lead 52 for connection to the stimulation port 59 of IPG 55as shown in FIGS. 5 and 9. One or more stimulation pulses are deliveredto the electrode 65 by the IPG 55 and transferred to the nerve resultingin opening of the airway during respiration. It should be readilyapparent to one skilled in the art that any suitable electrode forstimulating the desired muscle may be utilized with the stimulationsystem 50 according to the present invention. For example, the electrodemay be a full cuff electrode or any other electrode configuration forcapturing a respiratory motor nerve, such as the hypoglossal nerve.Further, with respect to any other neuromuscular stimulation systemswhich may benefit from the present inventions described herein, theelectrode(s) may include any electrode(s) that provide the desiredstimulation for such systems.

The IPG 55 includes signal processing circuitry 200, including detectionalgorithm or control logic 216, as shown in block diagram form in FIG.12a, respectively, and functionally shown in the flow diagrams of FIGS.13a-13g. The signal processing circuitry 200 processes the respiratoryeffort signal provided by the pressure sensor 60, such as pressuresensor assembly 115, and provides inspiration synchronized stimulationvia electrode or electrode system 65 for the treatment of respiratorydisorders.

To achieve adequate treatment of sleep apnea, the stimulation isinitiated by detection of inspiration onset, for example, within apredetermined time of the actual physiological onset, for example 200ms. Sensing onset 200 ms early (i.e. `predictive`) is desired.Stimulation is terminated as a function of a detected inspirationoffset. Slight errors of approximately 300 ms or less in timing causingearly offsets, late offsets, or early onsets are typically permitted bythe treatment system. Late onsets, however, are preferably no laterthan, for example, 200 ms. The requirement that detection of onsets beno later than, for example, 200 ms, is necessary to avoid airwayobstruction prior to stimulation. The timing to recruit a muscle toovercome obstructions which occur prior to stimulation force such arequirement. The present invention provides means for predictivelydetecting onsets to meet this requirement. In addition to rigid timingrequirements, the detection algorithm operates reliably in the presenceof cardiac artifacts and motion artifacts.

The description herein is set forth in a manner such that stimulationfor treatment of sleep apnea occurs substantially continuously andsynchronous with inspiration throughout the treatment period, except fortime of nonstimulation such as suspension, dose, therapy delay, etc. asdetermined by the algorithm described below. The treatment period is thetime period from when the treatment is turned on to when the treatmentis turned off. However, many of the concepts described herein areequally applicable to sleep apnea treatment systems wherein the onset ofapnea is detected in some manner and stimulation only performed aftersuch detection of apnea. For example, waveform analysis could beperformed to determine when an apnea is about to occur and thentreatment by stimulation could be initiated using concepts describedherein. Such detection of the onset of sleep apnea is described in U.S.Pat. No. 5,483,969 to Testerman et al. which is incorporated herein byreference in its entirety.

The detection algorithm or control logic 216 of the signal processingcircuitry 200, which will be described in detail below, makessignificant reference to FIG. 14. Therefore, a brief description of FIG.14 is appropriate at this point to introduce the elements thereof andprovide a brief description of some of the functionality of the controllogic 216. FIG. 14 includes a normal respiratory effort waveform 500characteristic of the signal sensed by the pressure sensor 60, adifferential pressure signal 300, an illustrative stimulus window 400during which one or more pulses are generated for treatment of airwaydisorders synchronized with inspiration onset 501a and inspirationoffset 502a, and a refractory period illustration wherein a refractoryperiod (R) is defined during at least a part of the expiratory and pauseperiods 34 and 32 (FIG. 2a) of the respiratory cycle.

Further, FIG. 14 shows the respiratory period (T) which is representedas the period from inspiration offset 502a to inspiration offset 502b,the time of inspiration (TI) which is shown as the time from inspirationonset 501b to inspiration offset 502b, and a variety of thresholds whichare utilized by the detection algorithm/control logic 216 to control andprovide inspiration synchronous stimulation. Such thresholds includeanalog onset threshold 520 and ΔV (i.e. slope) onset threshold 522 usedfor detection of inspiration onset, analog offset threshold 524 and ΔVoffset threshold 526 used for detection of inspiration offset (i.e.latched offset), Vref threshold 530 or zero crossing threshold used forvalidating or declaring a detected latched inspiration offset, and AGCamplitude threshold 528 used in updating gain of the respiratory signalfrom the sensor 60.

ΔV is representative of the slope of the respiratory effort waveform500. For illustration, the ΔV values can be generated by sampling thesensor output during a sample period, such as for example every 10 to 70ms. The sampled value is then compared to the previously sampled valueto obtain the net change in voltage (i.e. change in intrathoracicpressure) over the sample period. The net change, ΔV, is thus thepressure signal slope and therefore, representative of slope of therespiratory effort waveform.

The normal respiratory effort waveform 500 shows the amplitudes andslopes which are characteristic of inspiration onset and offset. Thepolarity of the voltage respiratory effort waveform 500 in FIG. 14 isinverted with respect to the polarity of the actual physiologic pressuremeasured by sensor 60. Inspiration is represented as a positive goingvoltage which indicates a negative inspiration pressure. Expiration isshown as a negative going voltage which indicates a positive expirationpressure. The stimulation system 50 includes automatic gain control(AGC) that references or normalizes the respiratory effort signal. Forexample, the signal may be normalized such that the positive signal peakis 1.2 volts, baseline (Vref) is 0 volts (DC), and the negative signalpeak is at approximately -1.2 volts. In other words, a 2.4 peak to peaksignal is provided. The AGC is described in further detail below and isapplicable to any variable input signal characteristic of a periodicphysiological parameter and is not limited to only the respiratoryeffort pressure signal described herein. The normalization of suchsignals is particularly advantageous when used in systems where timingdetection is based on comparison to signal thresholds.

Inspiration onset 501 is characterized as a rapid change in slope at anamplitude above a predetermined level, i.e. analog onset threshold 520(FIG. 14), and is detected by the control logic of the present inventionas a function of such characterization. Inspiration offset 502 ischaracterized by a negative change in slope above a predeterminedamplitude, i.e. analog offset threshold 524 (FIG. 14). A sustainednon-positive slope and an amplitude above the predetermined amplitudetypically indicate an offset 502 and an offset is detected and latchedby the control logic of the present invention as a function of suchcharacterization.

Physiological artifacts caused by cardiac pressures and body motions addcomplexity to the respiratory effort waveform. Cardiac artifacts produceslope changes very similar to onset and offset slope changes. However,the slope is not typically sustained for the same duration. Therespiratory amplitude level is typically not altered by the cardiacartifacts. Therefore, the combination of sustained slope and amplitudeprovides information to differentiate between inspiration events (onsetsand offsets) and cardiac artifacts to avoid stimulation at the impropertime. The control logic, for example, by using consecutive ΔV samples todetect offsets and onsets, utilizes such characteristics to preventmisdetection of valid onsets and offsets, i.e. offsets and onsets thatare not artifact onsets and offsets.

Motion artifacts are similar to inspiration in both sustained slope andamplitude. FIG. 15 displays a motion artifact 542 on a respiratorywaveform 540. Depending on the source of the artifact (slow or fast bodymovement, etc.) the slope and amplitude may be sufficient to satisfy thecharacteristics of either an inspiration onset and/or offset andstimulation based on such an artifact is to be avoided. As illustratedin FIG. 15, the control algorithm in accordance with the presentinvention utilizing a defined refractory period minimizes stimulationfrom occurring based on artifacts like artifact 542. Such distinguishingof the artifact from normal respiration will become apparent from thedetail description of the control logic 216 below.

The techniques used by the algorithm or control logic 216 to distinguishmotion artifacts are based on known physiological parameters ofbreathing during sleep. First, respiratory rate is known to be verystable and consistent during sleep. For example, a typicalbreath-to-breath rate variation of 15% has been established, withmaximum variations as high as 35%. Periods of wakefulness will have morebreath-to-breath variations, coughs, sighs, etc., but stimulation is notnecessary nor desirable while the patient is awake. The detectionalgorithm establishes the presence of a stable respiratory rate orrespiratory period in order for stimulation to occur when signal onsetcharacteristics are present, i.e. stimulation is suspended if a stablerespiratory rate or respiratory period is not detected. Second, as theratio between time of inspiration/total respiratory period (TI/T) isgenerally known, such as for example, between 0.30 and 0.40, arefractory period (i.e. blanking period after inspiration has occurred),that includes both hard and soft refractory periods, is utilized todetect or predict onset at a time just prior to the next expected onset.These two ideologies, along with others as will become apparent from thefurther detail below, are utilized by the algorithm to reject motionartifacts.

The IPG 55, shown in FIG. 9, is any IPG or stimulator capable of beingconfigured for control of stimulation as required herein for treatmentof sleep apnea. The IPG 55 may be, for example, a Medtronic nervestimulator sold under the trade designation ITREL II Model 7424 or aMedtronic nerve stimulator sold under the trade designation ITREL IIIModel 7425, both available from Medtronic Inc., Mpls., Minn., modifiedto include an input from the respiratory sensor 60 and modified toinclude all the signal processing capabilities as shown in FIG. 12a forcontrol of stimulation as required herein. Each of these nervestimulators include circuitry for providing a wide range of stimulationtherapies which can be used with the present invention. The stimulatorutilized should be capable of implementing the signal processing withminimum power consumption. Many various hardware configurations may beutilized to implement the described signal processing circuitry. Forexample, various designs incorporating hardware, software, processors,analog circuits, digital circuits, combinations of the aforementioned,etc. may be used to perform the necessary signal processing and thepresent invention is not limited to any particular configuration. AnyIPG 55 utilized requires an energy source.

The IPG 55 is implanted in the patient at a location such as shown inFIG. 5. However, any location normally utilized for implanting an IPGcan be used for the location of IPG 55 as would be readily apparent toone skilled in the art. A suitable implantable neurostimulator hasadvanced programmable features permitting mode changes by transcutaneousRF telemetry. The patient-controllable parameters of the IPG'soperation, such as the amplitude of stimulation, can therefore becontrolled by the patient through a small hand-held telemetry device,i.e. patient programmer 70, shown in FIG. 8. Likewise, the physician canpreset additional operational parameters of the IPG 55 through ahandheld telemetry device 81 of the physician programmer 80, as shown inFIG. 7, held over the implanted IPG 55.

As shown in FIG. 9, the IPG 55 includes two connector ports 58 and 59.The connector port 58 is for insertion of the sensor lead 57 and theconnector port 59 is for insertion of the stimulator lead 52.

FIG. 12a is a first embodiment of a block diagram of the processingcircuitry 200 that includes sensor input circuitry 201 necessary toacquire a respiratory signal from the pressure sensor 60 including meansfor biasing the sensor, filtering the sensor output and providing anormalized sensor signal. Processing circuitry 200 further includesmonitoring circuitry 203 for monitoring the sensed signal to synchronizestimulation with respiration.

In this first embodiment, as shown in FIG. 12a, a combination of analogand digital circuits is used. Logic functions are provided without useof a microprocessor, i.e. purely analog and digital circuits. The analogfront end or sensor input circuitry 201 for obtaining a respiratoryeffort signal includes sensor bias 202 required for biasing the pressuresensor 60. The pressure sensor 60, for example, the sensing element 126,requires a stable bias current in the range of 8.8 μA to 100 μA. Onemethod of sensor bias 202 includes providing a static bias current inthe range of, for example, 15 μA to 25 μA. Currents of this magnitudeprovide the best trade-off in terms of battery life and adequateimmunity from noise. Alternatively, a second manner of sensor bias 202includes providing a duty-cycled bias current. In this manner ofoperation, for example, a 80 μA to 100 μA bias is applied to the sensorjust prior to the sampling the respiratory signal. Such duty cyclingprovides lower power operation, i.e. saves battery life, and providesnoise immunity benefits.

The pressure induced AC voltage from the sensor 60 is AC coupled with ahigh pass filter pole at 0.1 Hz from the sensor bias current to a filter204, for example, a 2 pole, 3 Hz RC low pass filter. The filter 204 isfor anti-aliasing the signal prior to providing the signal to the AGCamplifier 206 and to remove the higher frequency edges ofnon-respiratory artifacts, such as cardiac artifacts, and also motionartifacts.

The AGC amplifier 206 (FIG. 12a) may operate at a sampling frequencyusing switched capacitor techniques or may be operated continuously. TheAGC amplifier 206 is responsible for normalizing the sensor output, suchas, for example, to a consistent 2.4 volt peak-to-peak signal. Theamplitude of this signal is then sampled and used by the analogthreshold comparator 212 for comparison to various thresholds and ispresented to the ADC 214 for conversion into digital delta voltagemeasurements (ΔV's) via the ΔV nulling amplifier 208 for providing anindication of the slope of the waveform. The outputs from the analogcomparator 212 and ADC 214 are then utilized by algorithm/control logic216 to provide inspiratory synchronous stimulation as further describedbelow.

The AGC amplifier 206 compensates for patient-to-patient andinter-patient respiration amplitude variabilities. For example, pressureamplitudes will vary as a patient changes sleeping positions. The AGCamplifier 206 provides adaptivity to the variable amplitudes and thusthe physician is not required to program a gain setting. The AGCamplifier 206 also makes the detection algorithm much easier toimplement as the thresholds, as described above and also further below,become relative to the normalized peak-to-peak signal and will operatethe same even as the true pressure varies throughout the night.

In the first embodiment of processing circuitry 200, the measurement ofthe pressure sensor signal amplitude is implemented in analog circuitry.The analog amplitude of the pressure signal is measured by comparison tovarious thresholds and digital outputs are provided to the detectionalgorithm 216 as a function of such comparisons. Because of the fixednature of the AGC amplitude threshold 528, the signal amplitude iseasily determined and readily comparable to the various analogthresholds in the analog domain. The one comparator 212 can bemultiplexed between the onset analog reference 520, offset analogreference 524, Vref threshold 530, and AGC analog reference 528. Asmention above, digital outputs are provided by the comparator 212 to thealgorithm/control logic 216 to indicate the crossing of such amplitudethresholds.

The sampled signal amplitudes of the signal from AGC amplifier 206 areused by the ΔV nulling amplifier 208 and ADC 214 to generate ΔV valuesof a desired bit size, for example, a 7 bit or 8 bit ΔV value.Configuring the amplifier prior to the ADC 214 and nulling the presentamplitude sample value with the previous sample amplitude value allowsfor digitally converting a change in voltage (i.e. slope) to ΔV's. Thenulling amplifier 208 has a gain, for example, of 16, to restoreamplitude to the differenced value. The ADC 214 sampling period issynchronized (non-overlapping) to the stimulus to avoid degrading theADC sensitivity with stimulus circuitry noise. The stimulatorfrequencies of the IPG 55 may be, for example, and thus the samplingfrequencies may be, for example, 20, 30, 33, and 40 Hz. One skilled inthe art will readily recognize that the ADC 214 and ΔV nulling andamplification block 208 could be switched, with the ADC 214 digitallyconverting the sampled amplitude to a digital value and the digitalvalues from the present sample and previous sample used to determine adigital ΔV value.

The ΔV values represent the change in amplitude over the samplingperiod. Several consecutive ΔV values can be evaluated to confirm thesustained slope characteristic of inspiration onset or offset asdescribed further below with reference to the detection algorithm. Byusing several, for example, two or more, consecutive ΔV samples, shortduration (higher frequency) noise or cardiac artifacts can be rejectedand thus misdetection of a valid onset or offset is avoided. Thetradeoff for considering more than one sample is that delay is added bywaiting to use multiple samples for detection of an onset or offset.

As an alternative to using digital ΔVs for representation of slope ofthe respiratory waveform to the detection algorithm 216, an analogdifferentiator and peak detector could be utilized for slopemeasurement. However, the availability of the ΔV's in the digital domainallows for precise threshold settings and variation in bandwidth bychoosing the number of samples to evaluate.

A second embodiment of signal processing circuitry 400 for performingthe signal processing with substantially equivalent results to signalprocessing circuitry 200 is shown in FIG. 12b. The sensor inputcircuitry, including the sensor bias 402, low pass filter 404, and AGCamplifier 406, is substantially the same as previously described withrespect to the first embodiment. However, the monitoring circuitry 203,as indicated by the dashed line in FIG. 12a, is performed with the useof a microprocessor 410 and associated code. The microprocessor 400includes an internal analog to digital convertor (ADC) 414 whichpresents a converted sampled amplitude to the algorithm/control logic416 and comparator 412, i.e. the logic and comparison are implemented insoftware. In this embodiment, ΔV's are still determined based on thesampled signal from the AGC amplifier representative of slope of therespiratory effort waveform, and sampled amplitude comparisons are stillmade with the various thresholds. However, the sampled amplitude of therespiratory effort signal is immediately converted to the digital domainby the ADC 414 and processed digitally by the algorithm to obtain theΔV's. Further, the digitally converted sampled amplitude is digitallycompared to digital thresholds 420, 424, 430, and 428 as necessary tocarry out the functions as described further below. The algorithm 416then processes the ΔV, i.e. slope, information which it generated, andthe amplitude comparison information generated by digital comparison412, as described further below. Also as described further below, theprocessor 400 can be powered down at certain times when it is notrequired; conserving energy. Although both the first and secondembodiment may be utilized in accordance with the present invention,along with various other configurations of digital or analog circuits,whether with the use of a processor or without, the remainder of thedescription shall be made with reference to FIG. 12a for simplification,except as otherwise noted and for specific features which areparticularly beneficial to the processor based configuration, such asprocessor power down.

The detection algorithm as shown in the flow diagrams of FIGS. 13a-13hshall now be described with reference thereto and with reference toother figures herein as required. The detection algorithm or algorithmlogic 216 as shown in FIG. 12a resides in the IPG 55 of the implantablesystem 50 shown in FIG. 5. The detection algorithm 216 detectsinspiration onset and offset using comparisons of sampled amplitude tomultiple thresholds and ΔV values representative of the slope of therespiratory effort signal. As described previously with reference toFIG. 12a, in the first embodiment, the digital outputs used by detectionalgorithm 216 to track the respiratory effort waveform, are the onsetand offset amplitude threshold comparison outputs from the analogcomparator 212 and the digital ΔV slope value output from the ADC 214(FIG. 12a). With respect to the second embodiment utilizing themicroprocessor and associated code, the digital comparison of thedigitally converted sampled amplitude to the various digital thresholdsalong with the ΔV values generated using the digitally converted sampledamplitude, all generated inside the microprocessor, are utilized by theprocessor control logic algorithm 416. This respiratory effort signalinformation concerning amplitude and slope and the knowledge ofrespiratory timing parameters during sleep are used by the algorithm toreject cardiac and motion artifacts and control stimulus of muscle inthe treatment of sleep apnea.

A top level flow diagram of the detection algorithm/control logic 216 isshown in FIG. 13a. Generally, the detection algorithm is initiated atIPG-ON (block 600).

The sensor signal is then sampled (block 610) at a programmed samplerate and the appropriate outputs (i.e. ΔV's and analog thresholdoutputs) are generated by the associated components of the system.Offset detection (block 620) and onset detection (block 700) are thenperformed, with offset detection taking precedence over onset detection.If neither offset nor onset is detected then the sensor signal isfurther sampled and offset and onset detection repeated. If offset isdetected, then various functions are performed such as determiningwhether suspension mode is to be entered, therapy delayed, or AGCupdated (blocks 640, 680). If onset is detected (block 700), thenstimulation is initiated (block 720). The stimulation is continued andthe sensor sampled during stimulation (blocks 730) until an offset isdetected (block 740) and stimulation is terminated (block 760). Thevarious functions performed after an offset is detected (blocks 640,680) are then performed.

The IPG ON command block 600 is a patient or physician controlledfunction, where he/she turns the IPG "ON" via the patient programmer 70or physician programmer 80. The IPG 55 recognizes the IPG ON command(block 602) and begins a start-up sequence including dose control timer(block 603), a dose delay (block 604), a setting of initial conditions606, and the entrance of suspension mode until a regular breathingpattern is recognized. The IPG ON command may also initiate a patientself stimulation test and/or a diagnostic self test, as describedfurther below.

Dose control timer (block 603) is immediately started by the on command,i.e., IPG-ON state. Dose is considered the treatment time over which theIPG 55 is on and stimulation synchronous with inspiration can occur asthe patient sleeps. A patient typically uses the system 50 during aregular night's sleep. A patient may sleep anywhere from, for example, 1to 15 hours. The dose period is initiated by the patient programmer 70or a physician programmer 80 transmitting an IPG-ON command to the IPG.Dose is terminated or dose timer timeout occurs by either reaching amaximum programmed dose time or the patient programmer 70 transmits anIPG-OFF command, i.e. IPG-OFF state. The dose time-out provides anautomated method for turning off stimulation in the morning after anight's sleep. The maximum dose time is physician programmable and maybe for example, from 1 hour to 15 hours in 1 hour increments.

The initial IPG-ON command also initiates the dose delay period (block604). The delay waits a sufficient amount of time before startingstimulation to allow the patient time to fall asleep. Dose delay 604 isphysician programmable from, for example, 0 to 75 minutes, in 5 minuteincrements. If stimulation were to start too soon, the patient may bedisturbed and may have difficulty sleeping. The detection algorithm doesnot operate during dose delay 604 and minimal battery power is consumedduring this delay period, for example, in a microprocessor based design,the microprocessor could be powered down.

At the end of the dose delay (block 604), the detection algorithmparameters are initialized (or reset). The initial conditions include:Onset Count=0, Offset Count=0, Artifact Count=0, Average RespiratoryPeriod Weighted Sum (TWS)=1 second, Max Stimulation On Timer=OFF. Inaddition, the start AGC watchdog timeout timer as described furtherbelow is initialized to 1 second and AGC gain is initialized to amid-gain setting as described further below. After initialization of theconditions (block 606), as indicated above, stimulus is indefinitelysuspended, i.e. suspension mode is entered, until a regular breathingpattern is recognized (block 608).

Generally as will be explained further below, in suspension mode,stimulation is disabled in the presence of artifacts or non-periodicrespiration. Suspension is defined as a state where stimulation issuspended due to the lack of a stable respiratory pattern. If thepresent measured respiratory period (T) is not within a specifiedminimum and maximum time or if it is not relatively equivalent, i.e.within a certain tolerance (Tvar) of, a stored weighted sum respiratoryperiod (TWS), then stimulus is suspended or suspension mode is entered.The detection algorithm does not exit suspension mode until a measuredrespiratory period (T) is within the allowed variability from theweighted sum respiratory period (TWS).

As shown in FIG. 13a, during the sampling of the sensor 60 (block 610),the detection algorithm looks for a valid onset so that stimulation canbe initiated (block 720). The onset of inspiration is characterized as asustained increase in slope greater than a physician programmable ΔVonset threshold value and an amplitude greater than a physicianprogrammable analog onset threshold as shown in FIG. 14. An offsetdetection takes precedence over onset detection, as reflected by OffsetLatched & Analog Vref block 622 (FIG. 13c).

As shown in block 700 of FIG. 13c, two consecutive ΔV's greater than thephysician programmed AV onset threshold value are required to indicate asustained increase in slope. The comparison of sampled ΔV's to the ΔVonset threshold is shown as block 704. The time required to obtain thetwo samples, for example, may be between 40 ms and 80 ms, depending onthe sampling rate; the stimulus rate and sampling rate being the same.The stimulus rate is programmed or fixed by the physician and the ΔVonset threshold can be adjusted at the same time to compensate forshorter or longer sampling rates. For example, a fasterstimulus/sampling rate would result in smaller ΔV's since less change isseen over the shorter sampling period. Thus, a lower ΔV onset thresholdmay be appropriate.

As shown in block 704, if a ΔV does not exceed the ΔV onset threshold,the onset counter for counting the number of times the ΔV onsetthreshold is exceeded is reset. If the ΔV onset threshold is exceeded,it is determined whether the stimulation has been suspended (block 706).Although a valid ΔV onset threshold level was detected, if the IPG 55 isin suspension mode, the onset counter is not incremented. Furthersampling and comparisons are then performed to detect offsets. Theoffsets are detected to determine if a stable respiratory signal ispresent. If the IPG is not in suspension mode then it is checked to seewhether the IPG is in refractory, i.e., a period of time between offsetdeclaration and onset as described further below. Refractory (R), asshown in FIG. 14, includes both a hard refractory (HR) and a softrefractory (SR), i.e. a final portion of refractory (R). Refractory (R)is a processed time, based on a preprogrammed percentage of measuredpatient respiratory periods (T), during which time the patient istypically denied access to stimulation, except possibly in softrefractory.

As shown in block 708, if the IPG is in refractory (R), then it ischecked to see whether it is in hard refractory (HR) or soft refractory(SR) (block 710). If the IPG 55 is in hard refractory (HR), the onsetcounter is not incremented and more ΔV comparisons are made. If therespiratory effort signal is in soft refractory (SR), then the amplitudeof the signal is compared to the programmed analog amplitude onsetthreshold (block 714). If the signal does not exceed the analog onsetthreshold, the onset counter is not incremented but rather reset to zeroand sampling is continued. If the signal exceeds the analog onsetthreshold, then the onset counter is incremented (block 716). Also asshown by blocks 708 and 712, if the AV onset threshold is exceeded andthe IPG is not in the refractory period, then the onset counter is alsoincremented (block 712). If the onset counter is equal to a count oftwo, a valid onset is declared (block 716), the counter is reset tozero, a stimulation timer is initiated for controlling the maximumstimulation length (block 718) as described further below, andstimulation is initiated (block 720).

The illustrative 200 ms onset previously described is obtainable,particularly by adjusting the programmable ΔV and analog amplitude onsetthresholds along with refractory (R) and soft refractory (SR) discussedfurther below. By such adjustment, the algorithm can be made to be`trigger happy` or predictive such that onset detection is not late andthe refractory (R) is maximized to save battery life. For example, withuse of the soft refractory period, the analog threshold may be set lowerto allow a lower signal to exceed the threshold and increment the onsetcounter. This still, however, blocks motion artifacts from beingdetected as an onset is detected only if both slope and amplitudethresholds are exceeded during soft refractory, as opposed to just slopeout of refractory (R).

Generally, to declare an onset and thus start stimulation, in additionto the ΔV onset threshold being exceeded by two consecutive samples, thealgorithm must be out of refractory (R) during the two consecutive ΔVsamples above threshold or the pressure signal amplitude must be greaterthan the analog amplitude onset threshold and the algorithm must be insoft refractory (SR). Further, the algorithm must be out of dose delay,therapy delay, and suspension for stimulation to occur.

It should be apparent to one skilled in the art, that variations ofonset detection may provide suitable detection. For example, the numberof counts may vary, the sampling rate may vary, more ΔV values may beused alone to detect onset in soft refractory as opposed to the use ofboth ΔV and amplitude information in soft refractory and other variationas would be readily apparent to one skilled in the art.

During stimulation, the sensor signal is still being sampled (block730). Offset detection (block 740) is being performed using the sampledsignal during stimulation (block 740). If an offset is detected andlatched while stimulation is on, stimulation is terminated (block 760)when the latched offset is validated or declared a valid offset. Ifoffset is not detected, stimulation proceeds until a maximum stimulationperiod is reached as timed by max-stimulation on timer (block 718), atwhich time an offset is automatically declared.

Therefore, maximum stimulation time is used in the event that an offsetof the inspiratory phase is not detected. A maximum stimulation timeshall terminate the stimulation and algorithm functions which typicallyoccur at a regularly detected and validated offset are initiated. Inother words, if maximum stimulation time is reached, an offset isdeclared and functions such as calculating weighted sum, startingrefractory, etc. are initiated. When an offset is detected and latched(block 740) and stimulation is terminated (block 760) after the latchedoffset is validated, the algorithm proceeds to suspension, artifact,therapy delay block 640 as will be described further below.

The detection and declaration of an offset during stimulation (block740) and when stimulation is off (block 620) shall be describedtogether, as the flow of both blocks is substantially similar with theexceptions as noted. Such description shall be set forth with referenceto FIGS. 13d and 13e.

Inspiration offset is the most reliable and repeatable signalcharacteristic to detect as the respiratory waveform slope changes froma positive slope to a sharp negative slope and the amplitude of therespiratory waveform signal reaches a peak value which is controlled bythe AGC, for example, the 1.2 volts. Therefore, detection algorithmoperation and timing is centered around the detection of offsets,although other periodic events in the respiratory signal may also beused.

Respiration timing, AGC control, and the accuracy, for example, of theprediction of the next onset are all dependent on offset detection.Generally, the detection of offset requires three consecutive ΔV samplesbelow the physician programmed ΔV offset threshold 526 (FIG. 14) and thefirst of the three ΔV samples is required to have an amplitude greaterthan the analog amplitude offset threshold 524 (FIG. 14). Once theserequirements are achieved, an offset is detected and latched. Thealgorithm then waits for the respiratory effort signal level to fallbelow the Vref or zero crossing threshold 530 before validating thelatched offset, i.e. declaring a valid offset and terminatingstimulation. Waiting for the signal to fall below the Vref threshold 530discriminates against cardiac artifacts riding on the signal, which maycause another offset to be prematurely detected. Alternatively, theoffset could also be validated at any amplitude after the offsetrequirements are met, such as for example, onset threshold or evenimmediately upon latching the offset.

With reference to the flow diagram of FIG. 13d, as the sensor signal issampled during stimulation (block 730), if an offset has not beendeclared or validated (block 742) and the maximum stimulation on timefor stimulation has not been reached (block 744), a comparison of ΔVsamples to the programmed ΔV offset threshold 526 is performed (block746). If the programmed ΔV offset threshold is not met, then thealgorithm resets the offset counter to zero and sample and comparisoncontinues. If the programmed ΔV offset threshold is met, then the stateof the offset counter is queried (block 748). If the offset count is atzero and the analog respiratory effort signal is not greater than theanalog offset threshold to produce a first offset count (block 750),then the offset counter is reset to zero, the offset counter is notincremented and sampling and comparison is continued to detect anoffset. If the offset count is equal to zero and the analog respiratorysignal is greater than the analog offset threshold, then a first countis made (block 752). If the offset count is not equal to zero (i.e., afirst offset count has been made), then such consecutive ΔV samples thatmeet the ΔV offset threshold increment the offset counter (block 752).If the counter registers three consecutive counts during threeconsecutive sample periods (block 754) with the first offset crossingthe analog offset threshold 524, an offset is detected and latched. Oncethe amplitude falls below Vref (block 742) the latched offset isvalidated and stimulus is terminated. If the three consecutive offsetcount requirement is not met, then the offset counter is reset, andsampling and comparison is continued for detecting offsets.

The offset declared or validated is then processed further bySuspension, Artifact, Therapy Delay block 640 and an offset hysteresistimer is started (block 758). Offset hysteresis is utilized to preventartifacts from declaring two offsets in a very short period of time. Forexample, if the offset slope was too shallow, multiple offsets could betriggered by artifacts in the signal waveform (e.g., if 6 consecutiveΔV's satisfied the ΔV offset threshold and the analog offset thresholdwas met for at least the first of each set of three, then two offsetscould be declared). Therefore, offset hysteresis provides a blankingperiod, for example, about 475 ms, after an offset has been declaredduring which no other offset can be declared. The blanking period is toprovide a form of hysteresis such that the algorithm will only `see` oneoffset per respiratory cycle. The offset hysteresis should besufficiently short to resume the detection of possible artifact signalsfor proper suspension mode and artifact counting operation.

Various alternatives to the offset detection portion of the algorithmcan be made. For example, the number of counts necessary for an offsetto be detected may be modified, the analog threshold may be required tobe satisfied for all three ΔV samples as opposed to just one, thesampling rate may be different, different levels of analog thresholdsmay be used for declaration or validation of an offset to terminatestimulus and any other variation may be made that would be apparent toone skilled in the art.

The offset detection when stimulation is off (block 620) issubstantially the same as described above with the exception thatmaximum stimulation on time does not need to be checked (block 744) asstimulation is off.

As mentioned previously, the detection algorithm/control logic 216 usesat least two ideologies including that the respiratory period (T) ofrespiration is known to be stable and consistent during sleep and thatthe ratio of the time of inspiration (TI) to the respiratory period (T)is typically known or can be evaluated with statistical measures. Thedetection algorithm 216 uses at least these two ideologies and alsorespiratory timing statistics of sleeping humans to make the algorithmrobust and exclusionary of misdetecting artifacts for onset and offset.As part of implementing the ideologies, the weighted sum respiratoryperiod (TWS) is used to build a running average of measured patientrespiration periods (T) and is utilized in connection with variousalgorithm functions to control stimulation and reject artifacts. Thevarious functions which employ the use of TWS include refractory(R)/soft refractory (SR) function, suspension function, AGC control, andthe artifact counter function. After a general discussion of the thesefunctions, the suspension function, AGC control and artifact counterfunction will be described further with reference to the flow diagram ofFIG. 13f and 13g. The use of refractory (R)/soft refractory (SR)function has been previously described with reference to the flowdiagram for onset detection (FIG. 13c).

The detection algorithm 216 evaluates the equivalence of every patientrespiration period (T) by comparison of measured periods (T) to thecontinuously calculated weighted sum respiratory period (TWS) and tobounds for a respiratory period to evaluate whether respiration isstable. The detection algorithm having knowledge of the weighted sumrespiratory period (TWS) and a substantially constant inspiration time(TI), also approximates the time between each offset and onset such thatonsets can be predicted.

The geometric-series weighted sum used to generate the weighted sumrespiratory average (T) is weighted more heavily by the most currentmeasured T periods. The algorithm adds the present weighted sum to thepresent T period and then divides by 2. The result is expressed in thefollowing equation: T Weighted Sum (n)= T Weighted Sum (n-1)+T Interval(n)!/2. The maximum number of T periods contained in one sum is ten, butthe T periods beyond the fifth have an insignificant contribution to thesum. Not all measured T periods are utilized in determining TWS. Thealgorithm measures the patient respiratory period (T) at each offset. IfT falls out of the predetermined bounds set for T, i.e. Tmin and Tmax,for example, in the range of 1 second to 16 seconds, indicatingnonperiodic respiration, then the algorithm will consider the T periodinvalid. The invalid T periods are not added to the weighted sum (TWS).

With the weighted sum average respiratory period (TWS) calculated, therefractory period (R) can be approximated as described below. Onsets(and thus stimulation) can be kept from occurring for a period of timein the refractory period (R) following the declaration of offset ofinspiration. This time frame is in the expiration phase of respiration.Any physiologic or sensor disturbances (artifacts, noise, etc.) duringthis time period can be rejected as onsets. Stimulation is thusinhibited during at least a portion of refractory (R), but samplingcontinues in order to detect the presence of artifacts and entersuspension mode, if necessary.

The refractory period (R) begins at the offset of inspiration (i.e. theend of stimulus) and continues almost until when the next inspirationonset is expected. A percentage of the weighted sum (TWS) is used tocalculate the refractory (R) duration. For example, with TI/T rangesknown from, for example, statistical analysis, the expiration portion ofrespiration and thus the refractory period (R) can be calculated as afraction of the weighted sum (TWS). For example, the calculatedrefractory period (R) may be implemented based on the weighted sum bymultiplying a physician programmable refractory multiplier of 0.375,0.50, 62.5, or 0.75 times the weighted sum: refractory (R)=(RefractoryMultiplier×Respiratory Period Weighted Sum (TWS)). Such particularrefractory multipliers are for illustration only and any portion of Tmay be designated as refractory, such as from 0.1 to 0.75, particularlydepending upon the individual patient's respiratory cycle.

The weighted sum respiratory period (TWS) is initialized upon the oncommand for the IPG 55 to be 1 second. The algorithm remains insuspension mode as described further below until the TWS is equivalentto the present measured T, i.e. periodic respiration is determined. Thealgorithm does not use refractory (R) to blank onsets until suspensionmode is exited. This insures that the weighted sum (TWS) will haveestablished a valid value and thus the refractory (R) will also be avalid duration for predicting onsets and blanking artifacts.

Refractory (R) is limited to a minimum time. This is achieved by onlyupdating the weighted sum (TWS) for T periods greater than 1 second andtherefore the weighted sum (TWS) has a minimum of 1 second. As such therefractory (R) minimum time is given by: Minimum Refractory=(RefractoryMultiplier×1 second). The establishment of a minimum refractory time isa safety guard against over stimulation by establishing some minimum ofblanking time.

Soft refractory (SR) is implemented in the final portion of therefractory period (R). The other portion of refractory (E) is referredto as hard refractory (HR) and is shown in FIG. 14. In hard refractory(HR), stimulation is not allowed, i.e. onsets are not responded to. Inthe soft refractory (SR) period of refractory (R), as shown in FIG. 14,an onset (i.e. stimulation) is allowed if the analog onset threshold andthe ΔV comparison as described with reference to FIG. 13c both indicatean onset. The soft refractory (SR) portion of refractory period (R) maybe a fraction of, for example, 12.5% of the weighted sum (TWS).Therefore, for illustration, if refractory (R) is 75% of the weightedsum, then the soft refractory (SR) is during the 62.5% to 75% portion ofrefractory (R).

Alternatively, the soft refractory (SR) could be a function orpercentage of refractory (R). Further, the refractory functions may bebased on stimulus duration as opposed to respiratory rate. With thisalternative, the algorithm would measure the duration of the previousstimulus interval and multiply the interval by a predetermined value. Afurther alternative for refractory could be based on both stimulusduration and the respiratory period (T) or any other alternativerespiratory timing parameter that would be suitable for defining arefractory, hard refractory, and/or soft refractory period followingoffset detection, such as TI.

Suspension mode, which also utilizes TWS, provides several benefits. Forexample, the suspension function keeps the patient from being overlystimulated, i.e. patient comfort. Further, this technique also conservesenergy to increase battery life. In suspension mode, stimulation isdisabled in the presence of artifacts or non-periodic respiration.Suspension is defined as a state where stimulation is suspended due tothe lack of a stable respiratory pattern. If the present measuredpatient respiratory period (T) is not within a specified minimum andmaximum time or if it is not relatively equivalent to, i.e. within anallowed variability of, a stored weighted sum respiratory period (TWS),then stimulus is suspended, i.e. suspension mode is entered. Thedetection algorithm does not exit suspension mode until a measuredpatient respiratory period (T) is within the allowed variability fromthe weighted sum respiratory period (TWS). The programmable values ofallowed T variability (hereafter referred to as Tvar) may be forexample, 25%, 33%, 50%, and infinite. Each and every offset isconsidered as a measure of the respiratory period (T) and/or thepresence of artifacts. While in suspension mode, the algorithm continuesall other signal processing tasks such as threshold comparisons, AGCadjustments, and weighted sum calculations.

Generally, suspension is entered by the algorithm under the followingconditions indicative of nonperiodic respiration. First, uponinitialization of the IPG 55, the algorithm is in the suspension state,as shown in FIG. 13b, block 608, after the IPG 55 is turned ON and dosedelay (block 604) is completed. Second, if the presently measuredrespiratory period (T) is less than the minimum or greater than themaximum bounds programmed for T, suspension mode is entered, i.e. thebounds of 1 second and 16 seconds as previously mentioned. Third, if thepresent respiratory period (T) is not within a programmed allowedvariability, i.e. Tvar, suspension mode is entered. And last, suspensionis entered after the completion of a therapy delay initiated with use ofthe artifact counter as described below. It should be readily apparentto one skilled in the art that the number of respiratory violations of,for example, Tmin, Tmax or Tvar, which are required for suspension modeto be entered may vary. For example, more than one violation may berequired to enter suspension.

The above described suspension mode technique disables stimulus in thepresence of physiologic artifacts such as arm movements and headmovements. Such movements occur only when the patient is in shallowsleep or awake. An example of the benefit of suspension mode is the caseof a sleeping patient awakening to a phone call. Suspension mode will beentered as the patient moves about and stimulation will be inhibitedwhile the patient speaks on the phone. Suspension mode is also intendedto disable stimulus in the presence of non-physiologic and environmentalnoise sources. During suspension mode, the algorithm continues toevaluate the signal and will exit suspension mode and return to stimulusas soon as a periodic respiratory signal is reestablished. Therefore,only the prevention of stimulus conserves energy as the sensor muststill be operated.

As mentioned above, an artifact counter is used to initiate a therapydelay during which time stimulation is disabled. This is technique alsoconserves energy, lengthens battery life, and rejects artifacts. If therespiratory waveform continues to be too variable or multiple motionartifacts are occurring while in suspension mode, then the artifactcounter will cause the algorithm to enter therapy delay. While insuspension mode, the number of offsets are counted by the artifactcounter, in which case an offset is defined as the falling peak ofeither a respiratory or artifact event. If a maximum number of offsetsare counted during suspension mode, then the algorithm enters a therapydelay period. The maximum artifact count is physician programmable, forexample, to 10, 20, 40, or 80. During therapy delay, initiated by theartifact counter, the algorithm does not process the respiratorywaveform signal and therefore, energy is conserved by turning thepressure sensor off and by preventing stimulation. Upon completion ofthe therapy delay period, the algorithm resets to an initial state (AGCgain and weighted sum reset, etc.) like when the IPG 55 was first turnedon. Sampling the signal in the suspension mode is then resumed.

The counting of offsets during suspension mode is a simple method fordetermining the extent of non-respiratory activity. If frequent offsetsare occurring, then this indicates that extensive movement exists andthe algorithm shall transition quickly into therapy delay. If suspensionmode occurs due to a short duration event, the offset artifact countwill not reach the maximum, and stimulus will resume after the steadyrespiration rate has been re-established. If suspension mode ismaintained by a variable respiratory rate, the offset artifact countwill eventually lead to a maximum artifact count and therapy delay fromcounting of offsets. It should be noted that the artifact count is resetto zero upon exiting suspension mode.

The artifact counter function also provides the patient a method toquickly terminate stimulation without the use of the patient programmer70. This is accomplished by tapping in the proximity of the pressuresensor to induce artifact counts. Such tapping allows the patient toterminate stimulus for the duration of therapy delay in the event thatthe patient programmer 70 is lost or fails during the night. Suchtermination could also be accomplished by use of a magnet being passedover a reedswitch built into the IPG 55.

Offset hysteresis, as previously described, is also used to conserveenergy, as during this period of time the sensor can be shut down.Further, although some functions described herein may depend on thesensor functioning during refractory, with some modifications to thealgorithm, the sensor may also be shut down during refractory,particularly hard refractory, as stimulation is prohibited. Thus, energycan also be conserved by shutting down the sensor whenever therespiratory waveform is not needed by the remainder of the system.

With reference to FIG. 13f, the flow of the suspension and artifactcounting techniques in the detection algorithm shall be described. Ifoffset is detected while stimulation is off (block 620), then it isdetermined whether the algorithm is in suspension as described above. Ifthe unit is in suspension mode, artifacts (i.e. offsets, bothinspiratory and artifact) are counted to determine if the algorithmshould go into therapy delay (block 644). If the count exceeds somepredetermined number, such as, for example, 16 counts, then the artifactcounter is reset to zero, suspension mode is exited and activation ofprogrammed therapy delay is entered (block 666). The therapy delay timeis also started upon receiving the IPG on command during either analready occurring therapy delay (block 666) or dose delay (block 604)(FIG. 13b). After the therapy delay is exited, the initial conditionsare set, substantially the same as when the IPG is turned on with thepatient programmer (FIG. 13b).

If an offset has been detected either during stimulation or whenstimulation is off, respiratory period (T) is measured (i.e.offset-to-offset or the time from the last offset to the current offset)(block 648). The current measured respiratory period (T) is thencompared to Tmin and Tmax (block 650). If the current respiratory period(T) is not greater than Tmin and less than Tmax, then refractory (R) isstarted (block 652) based on a percentage of the previous weighted sumrespiratory period (TWS). Further, if three consecutive currentrespiratory periods (T) measured do not meet these requirements, thenthe algorithm goes into suspension mode and stimulation is not allowed,otherwise, artifact counter is reset to zero and suspension mode isexited.

If the current respiratory period (T) is greater than Tmin and less thanTmax, then the current measured respiratory period (T) is added to theweighted sum average respiratory period and a weighted sum (TWS) of theprevious breaths is calculated to determine a new average weighted sumrespiratory period (block 654). Refractory is started (block 652) basedon a percentage of the new average weighted sum, as updated. Further,the current respiratory period (T) measured is compared to the weightedsum from the previous offsets (i.e. the old weighted sum prior to theaddition of the current T) (block 656). If the current T is equivalent,i.e. meets Tvar, indicating periodic respiration, then the artifactcounter is reset to zero and suspension mode is exited. Otherwise, it isonce again determined if three current respiratory periods (T) measureddo not meet the Tmin, Tmax and Tvar requirements (block 658). As before,if three consecutive T's do not meet the Tmin, Tmax, and Tvarrequirements, then the algorithm goes into the suspension mode orsuspension mode is continued (block 670) and stimulation is not allowed,otherwise, artifact counter is reset to zero and suspension mode isexited (block 662).

The number of consecutive out of tolerance T's necessary to entersuspension mode is programmable. For example, the number can be set atone or other suitable values. Further, Tvar can be set to infinity whichoverrides the suspension feature and suspension is never entered.

In either case, whether suspension mode is entered or exited, theautomatic gain control (AGC) is continually utilized or adjusted (block680) as shall be described with reference to FIG. 13g. However AGC isnot operational during treatment delays, i.e. dose delay or therapydelay, as the pressure sensor need not be operated during this delaytime, conserving battery life. The AGC control described herein isapplicable to the provision of any signal characteristic of a periodicphysiological parameter for use in a therapy system. For example, thenormnalization provided by the AGC control is particularly applicable tosystems which perform functions based on comparing the signal to thethresholds.

The AGC amplifier 206 (FIG. 12a), as described previously, is requiredto normalize the pressure sensor output to a consistent peak to peaksignal, for example, 2.4 volt peak-to-peak signal. The operation of theAGC for the system 50 is dependent on the detection algorithm forsynchronizing gain increment and decrements. The AGC consists of aplurality of gain steps, for example, 64 gains steps. Gain isincremented exponentially such that each gain step increases by the samepercentage, for example, about 5.3%. However, gain may be performed byother than exponential techniques, such as, for example, techniques thatproduce equivalent increases as opposed to equivalent percentageincreases.

Generally, the AGC functions in the following manner. The gain isincremented or decremented once per respiratory period (T). The AGC gainis changed immediately following detection of a periodic event in thewaveform, i.e. a `true` offset. True offset is defined here so as toindicate those offsets which are likely to be from an actual, stableinspiration offset and not a motion artifact or irregular breathing. Thealgorithm determines an offset is true if it does not occur duringrefractory (R) (including both soft refractory and hard refractory), asduring refractory (R) it is assumed that the offset is an artifactoffset. Offsets resulting in a respiratory period (T) outside of thepredetermined bounds set for the periods, such as, for example, lessthan 1 second or greater than 16 seconds, are also considered invalid.

It is desirable to not change gain during refractory as the offsetswhich occur in this period may be of large amplitude, due to a motionartifact, and gain may be unnecessarily updated. Also, the refractorysets a limit on how fast the gain can be changed. Thus, if a rapid burstof artifacts occurs during refractory (R) then there will be no rapidchange in gain. If a burst of artifacts occurs while the algorithm isnot in refractory (R), then the first artifact will be considered anoffset and subsequent artifacts will not change the gain as they will bein refractory (R). Thus, rapid offsets can only change the gain onceduring a respiratory cycle, i.e. increment or decrement once. AGCcontrol is performed during suspension mode, along with offset detectionand refractory, as only stimulus is inhibited and an exceeding of theartifact counter results in a therapy delay while in suspension mode.

An AGC watchdog timer also forms a part of AGC control. The AGC watchdogtimer is reset each time a valid offset occurs resulting in the AGC gainbeing updated. The watchdog timer will otherwise time-out at, forexample, 1.5 times the respiratory period weighted sum (TWS) or in otherwords, the watchdog timer time-outs at 50% beyond the point where anoffset is expected. At time-out an AGC threshold is used to determine ifthe AGC gain should be incremented or decremented by one step. Thewatchdog timer will continue to time-out and increment or decrementuntil offsets begin occurring. The offsets then take control of the AGCoperation. Therefore, the watchdog timer gets the gain to a level suchthat offsets can be detected and normal AGC control via offsets can beestablished, particularly when the IPG 55 is first turned on.

The AGC is initialized to a mid-range setting. If this initial gain istoo low, the watchdog timer may have to cycle several times beforeoffsets begin to occur and equilibrium is reached. The watchdog timer isloaded with a predetermined time, for example, 1 second at theinitialization of the algorithm. Thus, the gain will increment one stepper second until offsets are achieved, unless the initialized gain istoo high, in which case each offset and/or the watchdog timer willdecrement the gain until equilibrium is reached. The AGC is reset orreinitialized at each exit of therapy delay or dose delay.

Generally, therefore, gain is updated when an offset is detectedfollowing onset, even while in suspension mode or gain is updated when awatchdog time out occurs if an offset is not detected within apredetermined period of time. However, offsets detected while inrefractory (R), whether or not in suspension mode, do not initiate gainupdate. Further, since offsets are not even looked for in dose delay ortherapy delay, AGC is not updated during this time period. Typically,after initialization, the gain is incremented with use of the watchdogtimer until valid offsets can be detected. Thereafter, the AGC typicallycontrols the gain by toggling between increments and decrements to keepthe gain at a particular level, i.e. the AGC threshold 528 (FIG. 14) andthe waveform is normalized.

The flow of AGC control 680 is shown in FIG. 13g. AGC is run virtuallysimultaneously with the determination after an offset is detected ofwhether the algorithm should be in suspension or not as describedpreviously with reference to FIG. 13f. As such, block 650 (FIGS. 13f and13g) appears in both flow diagrams. AGC is not performed until thecurrent measured respiratory period (T) meets the requirements of beinggreater than Tmin and less than Tmax (block 650), i.e. a somewhat stableperiodic signal is sensed. Further, AGC update is performed if Tvar isset to infinity (block 650), regardless of the Tmin and Tmaxrequirements, i.e. if Tvar is set to infinity then all requirements forT are disabled for suspension and AGC functions. If the gain is notupdated the sensor is continued to be sampled (block 610) and offset andonset detection is performed (blocks 620 and 700). If such requirementsare met, then it is determined whether the algorithm is in refractory(R). If the algorithm is in refractory (R), then the gain is not updated(block 684). If the algorithm is not in refractory, then gain is eitherincremented or decremented based on a comparison with a predeterminedAGC amplitude threshold (FIG. 14) (blocks 686 and 690). If the amplitudeof the respiratory effort signal is less than the AGC threshold at anytime since the previous update, then gain is incremented at, forexample, offset, watchdog timeout or any other periodic event in therespiratory cycle. If the amplitude of the signal is greater than thethreshold at any time since the previous update, then the gain isdecremented at offset, watchdog timeout or any other defined periodicevent in the cycle. The watch dog timer is reset at each and every AGCincrement or decrement. However, at any time when no offsets aredetected in a specified period of time, then the gain is incremented ordecremented using the watchdog timer, i.e. a time based on the weightedsum respiratory period (block 692).

Generally, therefore, for a signal characteristic of a periodicphysiological parameter, such as respiration, which include multipleperiodic cycles, gain is updated when a periodic event is detected. Thegain, however, is updated only once during a periodic cycle. Further, awatchdog timeout occurs if the periodic event is not detected and gainis updated even though a periodic event is not detected. Thus, the gainwill be adjusted once per periodic cycle upon detection of a periodicevent or at a watchdog timeout.

Other alternative methods of AGC implementation may be utilized with thepresent invention. For example, the AGC may adjust the amplifier gainafter each amplitude sample has been taken. The magnitude of the samplewould then be processed digitally to adjust the gain such that theamplifiers operate in mid-dynamic range. This technique has theadvantage of quick gain adjustments and continuous digital knowledge ofthe signal amplitude. However, the AGC would not provide normalizationand thus relative threshold measurements are not possible.

In general, the algorithm must be in the following state for stimulationto occur. A valid onset consisting of a certain number of AV's, forexample, two ΔV's, above ΔV onset threshold must be detected. Therefractory period (R) must be complete or the analog onset thresholdmust be crossed if the algorithm is in soft refractory (SR). Thealgorithm must not be in suspension mode and the algorithm must not bein either dose delay or therapy delay.

Further, any one of the following events will terminate stimulation: apredetermined consecutive number of ΔV's, for example, three consecutiveΔV's, below ΔV offset threshold with the first ΔV sample below the ΔVoffset threshold satisfying the analog offset threshold (the offset mustalso be validated by comparison to another threshold level such as zerocrossing); maximum stimulation time is reached; a patient initiatestherapy delay by giving another IPG on command when treatment is on; endof the dose timer period after a night's sleep; and an IPG-OFF command.Moreover, in general, implantable stimulation system 50, operates in thefollowing manner. At some point following the IPG 55 implant, thepatient will undergo a sleep laboratory evaluation where algorithmparameters, such as those programmable parameters described herein(onset and offset thresholds, refractory, dose times, etc.) areoptimized to achieve proper stimulation for the individual patient. Thestimulation parameters (amplitude, rate, and pulse width) are alsoadjusted to achieve the muscle stimulation necessary to overcomerespiratory obstructions. After being programmed by the physician, thepatient is provided with a hand-held patient programmer 70 which isprimarily used to turn the IPG ON and OFF each evening and morning,respectively. The patient programmer 70 also may provide the patientwith display indications regarding system information such as batterylife warnings, failed stimulus components, etc., and further may be usedto automatically initiate other diagnostic and stimulation testing asdescribed further below. The implanted stimulation system 50, uponinitialization of treatment, then utilizes the sensed respiration effortwaveform to detect critical points in the waveform to provideinspiration synchronous stimulation for treating respiratory disorder inaccordance with the algorithm as described above.

The system 50 can also be used for patients with central apnea, orpatients whose central nervous system provides no drive to breath.Central apneas often occur in obstructive sleep apnea patients in whatare call mixed apneas. To ensure effective therapy, the patient must bestimulated over the first breaths following the central apnea, in orderto prevent obstructive apneas. Patients with such conditions generate arespiratory effort waveform somewhat as shown in FIG. 16b or FIG. 16c ascompared to a normal respiratory waveform (FIG. 16a). Because of therelative flatness of the waveform, offset and onset detection isdifficult and almost unusable for providing stimulation to treat theupper airway condition. However, the detection algorithm can be adjustedto continue stimulation asynchronously when the signal amplitude becomessmall. By making the ΔV and analog onset thresholds sensitive to flatsensor signals, stimulation can be maintained for such a patient.Although offsets are not detected, the maximum stimulation time can beused to terminate stimulation. Further, stimulation occurs, i.e., turnson, either at the end of hard refractory (HR) or refractory (R). Theaverage respiratory period weighted sum (TWS) is approximatelymaintained by the repetitive stimulation occurring based on the maximumstimulation time and asynchronous stimulation will continue until thepatient's periodic respiration returns. Further, the maximum stimulationtime can be adjusted to forego overstimulation.

A central sleep apnea is shown in FIG. 16c. For example, the centralsleep apnea 802 may occur over a time period of 5 seconds to 30 seconds.As shown in FIG. 16d, stimulation is synchronized to inspiration duringthe first and second cycles of respiration prior to central apneaoccurring. Stimulation, in accordance with the present invention, thenoccurs for the maximum stimulation time 804 as offset is not detectedduring central apnea. The offset is then due to maximum stimulation timebeing reached. Refractory then occurs after the maximum stimulationtime, during which time no stimulation is allowed. This particularrefractory period 806 is shown by the time period between the twomaximum stimulation times during the central sleep apnea. During thistime, i.e. central sleep apnea, the AGC is operating by means of thewatchdog timer and/or the maximum stimulation time offsets which updategain when no inspiration offsets are detected for a particular period oftime. This operation of the AGC, increases the signal amplitude, andallows the algorithm to detect an onset with use of a smaller amplituderespiratory signal. Once a first onset is detected (or offset) thenstimulation can be continued synchronous with inspiration as opposed tostimulating based on maximum period of stimulation and refractory. Thisability to increase gain to detect offsets or onsets of a smallerrespiratory signal is important because the first breaths 800, FIG. 16cafter central apnea are typically shallow (low effort) and thus thealgorithm compensates for the low effort by increasing the gain of thesignal using the watchdog timer. The increase in gain 810 during thecentral apnea is shown in FIG. 16e.

The stimulation control using the detection algorithm described aboveand synchronized to the respiratory effort waveform allows for theprovision of a preprogrammed train of pulses, i.e., voltage, current,power, to the electrode 65 (FIG. 5) as shown in FIG. 17a. This train ofpulses, also referred to as a burst, stimulate the nerve/muscle, such asa muscle in the upper airway, the diaphragm, or any other muscles whichare suitable for use in treatment.

FIG. 17b shows characteristics of a typical train of pulses that isinitiated upon onset detection as previously described. The train ofpulses is shown to begin upon onset at an amplitude of about 75% of theprogrammed value. The amplitude is then ramped to 100% of the programmedvalue. This ramped function provides added comfort during the nervestimulation. However, alternatively, the train of pulses may be startedat any percentage of the programmed value or any percentage of theprogrammed value, i.e. 100%, 110%, 150%. The train of pulses ends uponthe declaration of an offset, when maximum stimulation time is reachedor the IPG off command is entered as described previously.

FIG. 17c shows the characteristics of the individual pulses within thetrain of pulses. Amplitude, the rate at which the pulses are deliveredand the width of the individual pulses all impact the stimulation of themuscle. Minimizing the programmable amplitude, pulse width and rate ofstimulation increases the longevity of the system. As one of ordinaryskill in the art will recognize there are various manners of providingthe train of pulses or a single pulse, and the present invention is notlimited to any particular manner of generating such pulses. Any suitablecircuit configuration for providing such pulses may be utilized, such asthose available with the ITREL platforms.

FIG. 18 shows the system 50, as shown in FIG. 5, including the IPG 55which is a processor based IPG such as shown in FIG. 12b, sensor 60, andlead/electrode 65. The microprocessor 410 as previously describedinternally includes ADC 414. The IPG also includes the other componentspreviously discussed including sensor bias 402, low pass filter 404, andAGC amplifier 406. Further included in the IPG 55 are telemetrycomponents 440 coupled to antenna 442, stimulus output circuit 434 anddigital to analog convertor (DAC) 432 which is used to produce thecorrect stimulus output amplitude for the system. The microprocessor410, in addition to controlling stimulation, also controls the sensorbias 402, AGC amplifier 406 and diagnostic self test functions asdescribed further below.

With reference to the system of FIG. 18, an energy conserving techniqueshall be described which is not only applicable to this particularsystem, but also to other implantable therapy systems, such as, forexample, drug delivery systems, other stimulation systems, and any othersystems which could benefit from such an energy conservation technique.The processor based IPG 55 enters an off state, i.e. a treatment periodis not occurring, as a result of various events. For example, the offstate in the system 50 is entered when the patient programmer 70 is usedto send an IPG off command via telemetry using the telemetry circuitryand antenna 442. Further, the treatment period may end as a result of adose timer timing out at the end of a dose period, such as in themorning after a nighttime treatment period, or the treatment period mayend as a result of some other event. In such cases, the microprocessor410 goes through a shut-down sequence and enters an off or `sleep` modeduring which it is not required to function.

The shut down sequence includes turning off power to all non-essentialcircuits of the system 50. Such non-essential circuits during the sleepmode include the amplifier 406, sensor bias 402, ADC 414, DAC 432, andstimulus output circuits 434. In the microprocessor based system, themicroprocessor can also enter the sleep mode or stop mode where verylittle current is consumed, but the microprocessor will awake when aninterrupt line is toggled. The telemetry block 440 remains on to listenfor telemetry communication, such as from the patient programmer 70, andthen wakes the microprocessor 410 when the external communication, i.e.telemetry command, is received. During operation of the sleep mode,energy is conserved.

This sleep mode can also be used with the IPG having processingcircuitry that is not microprocessor based. For example, the logiccircuits could be shut down or powered down. Further, methods other thantelemetry could be used to wake up the processor. For example, a patientheld magnet and a reedswitch trigger located in the IPG could be used,or a background timer in the IPG could be used to automatically turn theIPG on at a certain time. Further, as previously indicated above, thissleep mode could be used with other implantable therapy systems. Forexample, a blink stimulation system could enter sleep mode at night whenessential circuits are not used or a drug delivery system could usesleep mode when there is a period of time that the essential componentsare not needed.

The patient programmer 70, FIG. 8, and the physician programmer 80, FIG.7, communicate with the IPG 55 via telemetry. The physician programmer80 allows the programmable parameters of the system to be adjusted bythe physician to conform to the needs of the patient. Such programmingdevices are readily known to those skilled in the art. Examples of suchdevices are described in U.S. Pat. No. 4,236,524 to Powell et al., U.S.Pat. No. 4,250,884 to Hartlaub et al., U.S. Pat. No. 4,305,397 toWeisbrod et al., U.S. Pat. No. 4,323,074 to Nelms, U.S. Pat. No.4,432,360 to Mumford et al., and U.S. Statutory Invention RegistrationNo. H1347 to Greeninger et al., all incorporated herein by reference intheir entirety. For example, all the programmable parameters mentionedwith respect to the detection algorithm and also the stimulus pulseamplitude, stimulus pulse duration, stimulus pulse frequency, andstimulus ramp on/off times can be adjusted through the physicianprogrammer 80. In addition, the physician programmer 80 can be used toaccess any stored data and retrieve such data stored in the implantedsystem. For example, the patient's name, the code number of the hospitalor clinic, the prescription date, and the last follow-up date could bestored in hardware of the system. Further, patient compliance data,system performance data, diagnostic testing data could be accumulated bythe system and read out through use of the programmer 80. For example,the total time the power is on, total stimulation time for the patient,the number of power cycles or reset cycles, the average battery voltageand fault detection could be stored and retrieved through the physicianprogrammer 80.

FIG. 8 shows the patient programmer 70 for patient control of the system50. The control panel of programmer 70 includes on and off switches 71,75 which allow the patient to turn the system on or off. Turning switch71 on initializes the treatment period using the above described controllogic. The buttons 73 allow the patient to adjust the amplitude ofstimulation for comfort level and other controls could be added to allowthe patient to control other parameters such as, for example, pulserate, pulse width, delay times.

The power on switch 71 also may be utilized to initiate various selftest functions as well as initiating a dose delay (block 604) if thedevice is already operating. One self test function initiated by thepower on switch is a patient stimulation self test function, whereinwhen the patient turns the stimulation system on with the patientprogrammer 70 for a treatment period, i.e. before going to bed, thestimulator immediately thereafter automatically provides stimulation tothe patient, such as to the hypoglossal nerve. This stimulation may bebased on the maximum stimulation time or any other predetermined timeperiod. Such power on stimulation, gives the patient the ability toverify that the system is capable of stimulating properly. For example,the stimulation verifies that the nerve/muscle was captured, that thelead placement is correct, that the lead from the IPG 55 to theelectrode 65 is operative, and also that the IPG stimulator outputcircuits for providing the pulse are functioning properly. At any timeduring the treatment, if the patient did not think that the system 50was functioning properly, the patient could, by pushing the power onswitch, provide a stimulus to check the device. Further, the stimulationself test could be performed at IPG-OFF.

The patient stimulation self test is not only applicable to respiratorytreatment systems as described herein, but is equally applicable to anystimulation systems that provide patient treatment. For example, such aself test could be used with a muscle therapy or conditioning system, ablink electrode stimulation system, or any other neuromuscularstimulation system. With respect to the respiratory disorder treatmentsystem described herein which, for example, stimulates the hypoglossalnerve, the stimulation automatically provided provides stimulationsufficient to evoke tongue protrusion, which the patient senses and thuscan verify that the stimulator is on and stimulation is functional.

Any faults detected by the stimulator using the stimulation self test orby any of the other tests described herein, such as the diagnostic selftests, can be reported to the patient via the patient programmer 70.Further, since the patient by the power on stimulus has tested theadequacy of the stimulation, the patient can adjust the amplitude ofstimulation by buttons 73, for example, within certain bounds set by thephysician. This adjustment would allow the patient to increasestimulation amplitude if capture of the nerve was not occurring ordecrease amplitude of stimulation if adequate capture was occurring, inorder to increase battery longevity. Such patient adjustment may be usedfor any other physician programmable parameters that the physician wouldwant the patient to be able to control. For example, stimulus rate,pulse width, therapy delay periods, etc. Moreover, if the system is notfunctioning properly, a visit to the physician can be made forevaluation of the system, i.e. such as by accessing test data or faultdata stored in the system.

The power on switch 71 may also be utilized to initiate an internaldiagnostic self test for testing the system to determine whether thecomponents and circuit functions, along with the detection algorithm areoperating properly. However such diagnostic self test can also be runwhenever the system is not interactive with the patient. For example, adiagnostic self test of the system described with reference to FIG. 18could be run during a dose delay, a sleep mode, a therapy delay, atIPG-OFF or anytime during the day when the patient is awake. During thediagnostic self test, components and functions of the system can betested, for example, with reference to the system of FIG. 18, theamplifier 406, the filter 404, and all the rest of the components can betested as described further below. Typically, such testing is performedat the physicians office using the physician programmer 80. However,since this treatment is performed during the sleep period of a patient'sday, it may not be known whether the system is functioning properly ornot as the patient is asleep when it is operating. Therefore, adiagnostic self test during a period of time when the system is notinteracting with the patient, i.e. stimulation or sensing, or in otherwords when the patient is not dependent on the treatment, is beneficial.With, for example, a fault indication sent to the patient programmer 70when faults are detected, the patient has some assurance that the systemis functioning properly.

The diagnostic self test strategy as shown in FIG. 19, is applicable tomany different therapy systems. For example, as shown therein, a typicaltherapy system 900 includes a therapy device 901, i.e. IPG 55, having aninput circuit 908 for receiving an input such as a sensed signal 904 ofa patient 10. The device 901 further includes a microprocessor or someother logic circuitry 912 for processing the sensed signal andgenerating an output 906 via output circuit 910. Further, the device mayinclude telemetry circuitry 914 for receiving and transmittinginformation from and to an external source.

The general diagnostic test strategy for such a generally describedtherapy system, includes applying the generated output 906 from theoutput circuit 910 to the patient 10. The result of the therapy due tothe generated output 906 is sensed via the input circuit 908 to verifyoperation of the system. For example, a stimulus output, i.e. a cardiacpace, could be applied to the patient and the input circuit could sensewhether the cardiac pace resulted in a physiological response in thepatient. Further, for example, the stimulus output could be a train ofpulses to the genioglossus muscle to treat sleep apnea. The inputcircuit would then provide the sensed signal characteristic ofrespiratory effort to the microprocessor to verify that a correctrespiratory response was achieved with the stimulus of the genioglossusmuscle, i.e. open airway and proper respiratory action. If a correctresponse is not indicated, the system could be further tested. Aninternal attenuated feedback output 916 (shown as a thicker line thanthe lines of system normal configuration) from the output to the inputcan be used to determine if the input or output circuits are operatingproperly. This general test strategy will detect faults internal andexternal to the device 601. For example, a broken stimulus or sense leadcould be detected or a faulty output circuit could be detected.

FIGS. 20a-d show various block diagrams of other more specific internaldiagnostic self tests for testing various components of the system shownin FIG. 18. FIG. 20a shows the blocks of FIG. 18 involved in a front endamplifier self test. The DAC 432 sends a voltage or voltage pulse to theinput of filter 404, amplifier 406, or ADC 414. The microprocessor 410then verifies the correct response. The DAC 432 is also verified by itsparticipation in these loops.

FIG. 20b shows the blocks involved in a sensor bias self test. A biassignal from sensor bias 402 is directed to the ADC 414 and measured andcompared to set references by the microprocessor 410. A sensor signalfrom sensor 60, for example, a DC static voltage resulting from sensorbias, can also be directed to the ADC 414, measured and compared to setreferences by the microprocessor 410 for verification.

FIG. 20c shows the blocks involved in a stimulus output self test. Theoutput from the stimulus output 434 with its amplitude under control ofDAC 432 is directed to the ADC 414 and verified by the microprocessor410. The output can be ramped to its maximum stimulus and thenattenuated for input to ADC 414 for measurement.

FIG. 20d shows the blocks involved in a telemetry self test. Thetelemetry circuitry 440 can be tested in a couple of ways. First, knownvoltage pulses are applied to the telemetry circuit 440 via the DAC 432to drive the circuit, i.e. simulate a received ping, and telemetryreception is verified via the microprocessor 410 and a demodulatedvoltage measured on the ADC 414. Likewise, the microprocessor 410 couldinitiate a telemetry uplink, i.e. ping on antenna, and the ADC 414 willverify the signal on the antenna 442. Second, a telemetry uplink can beinitiated with the microprocessor 410, i.e. ping the antenna, and thenimmediately enable the telemetry demodulator of circuitry 440 to detectthe ringing of the antenna 442 with verification of the detectionperformed by the microprocessor 410. This second test would not use theADC 414 or the DAC 432.

Further tests could be performed to verify other components andfunctions. For example, the AGC could be calibrated by switching in aknown signal, analog offset and onset detection could be verified by aDAC generated signal, and lead and battery measurements could be made.Further, diagnostic self test results can be stored and uplinked toallow quick fault identification at either a patient or a physicianprogrammer.

It will be appreciated by those skilled in the art that while theinvention has been described above in connection with particularembodiments and examples, the invention is not necessarily so limitedand that numerous other embodiments, examples, uses, modifications anddepartures from the embodiments, examples and uses may be made withoutdeparting from the inventive concepts.

What is claimed is:
 1. A method of predicting critical points in patientrespiration, the method comprising the steps of:monitoring at least onecharacteristic of a respiratory effort waveform of a patient to detect arespiratory event; defining a refractory period including a hardrefractory period during which time the respiratory event cannot beresponded to and a soft refractory period following the hard refractoryperiod; detecting the respiratory event outside of the refractory periodas a function of a first set of predetermined parameters for themonitored at least one characteristic; and detecting the respiratoryevent within the soft refractory period as a function of a second set ofpredetermined parameters for the monitored at least one characteristic.2. The method according to claim 1, wherein the respiratory event isinspiration onset and further wherein the at least one characteristic ofthe respiratory effort waveform monitored is at least one of slope andamplitude.
 3. The method according to claim 2, wherein the step ofdetecting inspiration onset outside of the refractory period includesthe step of detecting inspiration onset outside of the refractory periodas a function of monitored slope of the respiratory effort waveform, andfurther wherein the step of detecting inspiration onset within the softrefractory period includes the step of detecting inspiration onsetwithin the soft refractory period as a function of monitored slope andamplitude of the respiratory effort waveform.
 4. The method according toclaim 1, wherein the refractory period is defined based on detection ofinspiration offset.
 5. The method according to claim 2, wherein therefractory period is defined based on detection of inspiration offsetand further wherein the method includes the step of detectinginspiration offset as a function of the monitored slope and amplitude ofthe respiratory effort waveform.
 6. The method according to claim 5,wherein the monitoring step includes sampling the amplitude of therespiratory effort waveform and generating slope values representativeof the respiratory effort waveform based on the amplitude samples, andfurther wherein the detection of inspiration offset includes the stepsof:comparing the slope values to a predetermined slope value offsetthreshold in a first comparison step; comparing the amplitude of thesampled respiratory effort waveform to a predetermined amplitude offsetthreshold in a second comparison step; detecting inspiration offset as afunction of the first comparison step and second comparison step.
 7. Themethod according to claim 6, wherein the detection of inspiration offsetfurther includes validating the detected inspiration offset by comparingthe amplitude of the sampled respiratory waveform to a validating offsetthreshold.
 8. The method according to claim 6, wherein the detectinginspiration offset step further includes the step of detectinginspiration offset if a predetermined number of slope values satisfiesthe slope value offset threshold and the amplitude of at least the firstof the predetermined number of slope values satisfies the amplitudeoffset threshold.
 9. The method according to claim 2, wherein themonitoring step includes sampling the amplitude of the respiratoryeffort waveform signal and generating slope values representative of therespiratory effort waveform based on the amplitude samples, and furtherwherein the detection of inspiration onset outside of the refractoryperiod includes the step of detecting an inspiration onset as a functionof a comparison of the slope values to a predetermined slope value onsetthreshold.
 10. The method according to claim 9, wherein the detection ofinspiration onset outside of the refractory period includes detectinginspiration onset if a predetermined number of slope values satisfy thepredetermined slope value onset threshold.
 11. The method according toclaim 2, wherein the monitoring step includes sampling the amplitude ofthe respiratory effort waveform and generating slope valuesrepresentative of the respiratory effort waveform based on the amplitudesamples, and further wherein the detection of inspiration onset withinthe soft refractory period includes the step of detecting inspirationonset as a function of a comparison of the slope values to apredetermined slope value onset threshold and comparison of theamplitude thereof to a predetermined amplitude onset threshold.
 12. Themethod according to claim 11, wherein the detection of inspiration onsetwithin the soft refractory period includes detecting inspiration onsetif a predetermined number of slope values satisfy the predeterminedslope value onset threshold and the amplitude thereof satisfies theamplitude onset threshold.
 13. The method according to claim 1, whereinthe defining step includes the steps of:detecting inspiration offset;determining an average respiratory period; providing an average time ofinspiration; and defining the refractory period, including the soft andhard refractory periods, as a function of the detected inspirationoffset, average respiratory period, and average time of inspiration. 14.The method according to claim 13, wherein the refractory period isdefined as a portion of the average respiratory period and the softrefractory period is defined as a portion of the refractory period. 15.The method according to claim 13, wherein the refractory period isdefined as a portion of the average respiratory period and the softrefractory period is defined as a portion of the average respiratoryperiod.
 16. The method according to claim 13, wherein the averagerespiratory period is a weighted sum average respiratory period.
 17. Themethod according to claim 1, wherein the refractory period is defined asa function of an average time of inspiration, the average time ofinspiration being a physician programmable value.
 18. The methodaccording to claim 1, wherein the defining step includes defining therefractory period, including the soft and hard refractory periods, as afunction of time of stimulation.
 19. The method according to claim 2,wherein the monitoring step includes sampling the amplitude of therespiratory effort waveform and generating slope values representativeof the respiratory effort waveform based on the amplitude samples, andfurther wherein the method includes setting an amplitude onset thresholdand a slope value onset threshold, and yet further wherein the detectionof inspiration onset outside of the refractory period is performed bycomparing the slope values to the slope value onset threshold and thedetection of inspiration onset within the soft refractory period isperformed by comparing the slope values to the slope value onsetthreshold and the amplitude thereof to the amplitude onset threshold.20. A method for providing stimulation of a patient to treat respiratorydisorders, the method comprising the steps of:monitoring slope andamplitude of a respiratory effort waveform of a patient to detectinspiration onset; defining a refractory period including a hardrefractory period during which time an inspiration onset cannot initiatestimulation and a soft refractory period following the hard refractoryperiod; detecting inspiration onset outside of the refractory period asa function of the slope of the respiratory effort waveform; detectinginspiration onset within the soft refractory period as a function ofslope and amplitude of the respiratory effort waveform; and stimulatingin response to a detected inspiration onset.
 21. The method according toclaim 20, wherein the refractory period is defined based on detection ofinspiration offset.
 22. The method according to claim 21, furtherincluding the step of detecting inspiration offset as a function of themonitored slope and amplitude of the respiratory effort waveform. 23.The method according to claim 22, wherein the monitoring step includessampling the amplitude of the respiratory effort waveform and generatingslope values representative of the respiratory effort waveform based onthe amplitude samples, and further wherein the detection of inspirationoffset includes the steps of:comparing the slope values to apredetermined slope value offset threshold in a first comparison step;comparing the amplitude of sampled respiratory effort waveform to apredetermined amplitude offset threshold in a second comparison step;and detecting inspiration offset as a function of the first comparisonstep and the second comparison step.
 24. The method according to claim23, wherein the detection of inspiration offset further includesvalidating the detected inspiration offset by comparing the amplitude ofthe sampled respiratory waveform to a validating offset threshold andterminating stimulation as a function of such comparison.
 25. The methodaccording to claim 24, wherein the validating offset threshold is one ofthe detected inspiration offset, zero crossing of the respiratorywaveform, or an inspiration onset threshold.
 26. The method according toclaim 23, wherein the detecting inspiration offset step further includesthe step of detecting inspiration offset if a predetermined number ofslope values satisfies the slope value offset threshold and theamplitude of at least the first of the predetermined number of slopevalues satisfies the amplitude offset threshold.
 27. The methodaccording to claim 20, wherein the monitoring step includes sampling theamplitude of the respiratory effort waveform signal and generating slopevalues representative of the respiratory effort waveform based on theamplitude samples, and further wherein the detection of inspirationonset outside of the refractory period includes the step of detecting aninspiration onset as a function of a comparison of the slope values to apredetermined slope value onset threshold.
 28. The method according toclaim 27, wherein the detection of inspiration onset outside of therefractory period includes detecting inspiration onset if apredetermined number of slope values satisfy the predetermined slopevalue onset threshold.
 29. The method according to claim 1, wherein themonitoring step includes sampling the amplitude of the respiratoryeffort waveform signal and generating slope values representative of therespiratory effort waveform based on the amplitude samples, and furtherwherein the detection of inspiration onset within the soft refractoryperiod includes the step of detecting inspiration onset as a function ofa comparison of the slope values to a predetermined slope value onsetthreshold and comparison of the amplitude thereof to a predeterminedamplitude onset threshold.
 30. The method according to claim 29, whereinthe detection of inspiration onset within the soft refractory periodincludes detecting inspiration onset if a predetermined number of slopevalues satisfy the predetermined slope value onset threshold and theamplitude thereof satisfies the amplitude onset threshold.
 31. Themethod according to claim 20, wherein the defining step includesdefining the refractory period, including the soft and hard refractoryperiods, as a function of time of stimulation.
 32. The method accordingto claim 20, wherein the stimulation is continued until at leastinspiration offset is detected or until a maximum stimulation time isreached.
 33. A method for providing stimulation of a patient to treatrespiratory disorders, the method comprising the steps of:monitoringslope and amplitude of a respiratory effort waveform of a patient todetect inspiration onset and inspiration offset; defining a refractoryperiod including a hard refractory period during which time aninspiration onset cannot initiate stimulation and a soft refractoryperiod following the hard refractory period; detecting inspiration onsetoutside of the refractory period as a function of a first set of atleast one of slope and amplitude criteria for the respiratory effortwaveform; detecting inspiration onset within the soft refractory periodas a function of a second set of at least one of slope and amplitudecriteria for the respiratory effort waveform; stimulating in response todetection of inspiration onset, stimulation terminating as a function ofdetection of inspiration offset or a maximum stimulation time; andsetting the second set of criteria sufficiently sensitive relative tothe first set of criteria such that stimulation, for one or morerespiratory cycles, is applied as a function of the maximum stimulationtime and the defined refractory period.
 34. The method according toclaim 33, further including the step of updating gain of the respiratoryeffort waveform during the one or more respiratory cycles such thatstimulation can be controlled by detecting inspiration onset duringlater respiratory cycles.
 35. A method of predicting critical points inpatient respiration, the method comprising the steps of:sampling theamplitude of the respiratory effort waveform of a patient; generating asample signal representative of at least one characteristic of therespiratory effort waveform based on each amplitude sample, monitoringthe sample signals representative of the at least one characteristic ofthe respiratory effort waveform; and detecting a respiratory event as afunction of at least two sample signals.
 36. The method according toclaim 35, wherein the respiratory event is inspiration onset, andfurther wherein the at least one characteristic of the respiratoryeffort waveform is at least one of slope and amplitude.
 37. The methodaccording to claim 36, wherein inspiration onset is detected as afunction of at least two sample signals representative of slope of therespiratory effort waveform.
 38. The method according to claim 35,wherein the respiratory event is inspiration offset and further whereinthe at least one characteristic of the respiratory effort waveform is atleast one of slope and amplitude.
 39. The method according to claim 38,wherein the generating step includes generating slope valuesrepresentative of the respiratory effort waveform based on the eachamplitude sample, and further wherein the detection of inspirationoffset includes the steps of:comparing the slope values to apredetermined slope value offset threshold in a first comparison step;comparing the sampled amplitude of the respiratory effort waveform to apredetermined amplitude offset threshold in a second comparison step;and detecting inspiration offset as a function of the first comparisonstep and the second comparison step.
 40. The method according to claim39, wherein the step of detecting inspiration offset further includesvalidating the detected inspiration offset by comparing the sampledamplitude of the respiratory waveform to a validating offset threshold,whereby the validated inspiration offset as opposed to the detectedinspiration offset triggers an associated activity.
 41. The methodaccording to 40, wherein the validating offset threshold is one of thedetected inspiration offset, zero crossing of the respiratory waveform,or an inspiration onset threshold.
 42. The method according to claim 40,wherein the detecting inspiration offset step further includes the stepof detecting inspiration offset if a predetermined number of slopevalues satisfies the slope value offset threshold and the amplitude ofat least the first of the predetermined number of slope values satisfiesthe amplitude offset threshold.
 43. An apparatus for predicting criticalpoints in patient respiration, the apparatus comprising:monitoring meansfor monitoring at least one characteristic of a respiratory effortwaveform of a patient; and respiration detection means for detecting arespiratory event, the respiration detection means including: means fordefining a refractory period including a hard refractory period and asoft refractory period following the hard refractory period; means fordetecting the respiratory event outside of the refractory period as afunction of a first set of predetermined parameters for the monitored atleast one characteristic of the respiratory effort waveform; and meansfor detecting the respiratory event within the soft refractory period asa function of a second set of predetermined parameters for the monitoredat least one characteristic of the respiratory effort waveform.
 44. Theapparatus according to claim 43, wherein the respiratory event isinspiration onset.
 45. The apparatus according to claim 44, wherein theat least one characteristic of the respiratory effort waveform monitoredis at least one of slope and amplitude of the respiratory effortwaveform.
 46. The apparatus according to claim 45, wherein therespiration detection means further includes means for detectinginspiration offset as a function of the at least one monitored slope andamplitude of the respiratory effort waveform.
 47. The apparatusaccording to claim 46, wherein the inspiration offset detection meansincludes:means for comparing the slope to a predetermined slope offsetthreshold; and means for comparing the amplitude of the respiratoryeffort waveform to a predetermined amplitude offset threshold.
 48. Theapparatus according to claim 45, wherein the means for detecting therespiratory event outside of the refractory period includes means forcomparing the monitored slope of the respiratory effort waveform to apredetermined slope onset threshold to detect inspiration onset.
 49. Theapparatus according to claim 45, wherein the means for detecting therespiratory event within the soft refractory period includes means forcomparing the monitored slope of the respiratory effort waveform to apredetermined slope onset threshold and means for comparing theamplitude of the respiratory effort waveform to a predeterminedamplitude onset threshold to detect inspiration onset.
 50. A system forproviding stimulation of a patient to treat respiratory disorders, thesystem comprising:a sensor for providing a signal characteristic of arespiratory effort waveform of the patient; slope monitoring means formonitoring the slope of the respiratory effort waveform; amplitudemonitoring means for monitoring the amplitude of the respiratory effortwaveform; respiration detection means for detecting inspiration onset,the respiration detection means including:means for defining arefractory period, the refractory period including a hard refractoryperiod during which time an inspiration onset cannot be responded to anda soft refractory period following the hard refractory period; means fordetecting inspiration onset outside of the refractory period as afunction of the slope of the respiratory effort waveform; means fordetecting inspiration onset within the soft refractory period as afunction of slope and amplitude of the respiratory effort waveform;means for generating a stimulation signal in response to a detectedinspiration onset; andat least one electrode for delivering thestimulation signal to the patient.
 51. The system according to claim 50,wherein the respiration detection means includes means for detectinginspiration offset as a function of at least one of monitored slope andamplitude, and further wherein the refractory period is defined based ondetection of inspiration offset.
 52. The system according to claim 50,wherein the means for detecting inspiration onset outside of therefractory period includes means for comparing the slope of therespiratory effort waveform to the predetermined slope onset threshold.53. The system according to claim 51, wherein the means for detectinginspiration offset includes means for comparing the slope of therespiratory effort waveform to a predetermined slope offset thresholdand means for comparing the amplitude of the respiratory effort waveformto a predetermined amplitude offset threshold.
 54. The system accordingto claim 50, wherein the respiration detection means further includesmeans for terminating stimulation after a maximum predeterminedstimulation time period.